General Information of the Disease (ID: DIS00108)
Name
Pituitary cancer
ICD
ICD-11: 2F37
Resistance Map
Type(s) of Resistant Mechanism of This Disease
  ADTT: Aberration of the Drug's Therapeutic Target
  EADR: Epigenetic Alteration of DNA, RNA or Protein
  IDUE: Irregularity in Drug Uptake and Drug Efflux
  RTDM: Regulation by the Disease Microenvironment
  UAPP: Unusual Activation of Pro-survival Pathway
Drug Resistance Data Categorized by Drug
Approved Drug(s)
8 drug(s) in total
Click to Show/Hide the Full List of Drugs
Bromocriptine
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Dopamine receptor D2 (DRD2) [1]
Resistant Disease Prolactin-secreting adenoma [ICD-11: 2F37.Y]
Molecule Alteration Expression
Down-regulation
Resistant Drug Bromocriptine
Experimental Note Identified from the Human Clinical Data
Mechanism Description Generally, the effectiveness of BRC or CAB has been related to a decreased expression in DRs, as the expression of such receptors has been shown to correlate with responsiveness to therapy in lactotroph, somatotroph, corticotroph and in clinically nonfunctioning PitNET.
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: hsa-miR-17-5p [2]
Resistant Disease Prolactin-secreting adenoma [ICD-11: 2F37.Y]
Molecule Alteration Expression
Up-regulation
Resistant Drug Bromocriptine
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell proliferation Activation hsa05200
In Vitro Model C4-2 cells Prostate Homo sapiens (Human) CVCL_4782
Experiment for
Molecule Alteration
Solexa sequencing assay; qRT-PCR
Experiment for
Drug Resistance
CCK-8 assay
Mechanism Description Overexpression of mir-93 increased resistance to bromocriptine and cabergoline treatment.
Key Molecule: hsa-mir-126 [2]
Resistant Disease Prolactin-secreting adenoma [ICD-11: 2F37.Y]
Molecule Alteration Expression
Up-regulation
Resistant Drug Bromocriptine
Experimental Note Identified from the Human Clinical Data
In Vitro Model KHM-5M cells Pleural effusion Homo sapiens (Human) CVCL_2975
Experiment for
Molecule Alteration
Solexa sequencing assay; qRT-PCR
Experiment for
Drug Resistance
Clinical diagnostic evaluation
Mechanism Description Hsa-mir-93, hsa-mir-17, hsa-mir-22*, hsa-mir-126*, hsa-mir-142-3p, hsa-mir-144*, hsa-mir-486-5p, hsa-mir-451, and hsa-mir-92a were up-regulated and hsa-mir-30a, hsa-mir-382, and hsa-mir-136 were down-regulated in bromocriptine-resistant prolactinomas in comparison with bromocriptine-sensitive prolactinomas.
Key Molecule: hsa-mir-136 [2]
Resistant Disease Prolactin-secreting adenoma [ICD-11: 2F37.Y]
Molecule Alteration Expression
Down-regulation
Resistant Drug Bromocriptine
Experimental Note Identified from the Human Clinical Data
In Vitro Model KHM-5M cells Pleural effusion Homo sapiens (Human) CVCL_2975
Experiment for
Molecule Alteration
Solexa sequencing assay; qRT-PCR
Experiment for
Drug Resistance
Clinical diagnostic evaluation
Mechanism Description Hsa-mir-93, hsa-mir-17, hsa-mir-22*, hsa-mir-126*, hsa-mir-142-3p, hsa-mir-144*, hsa-mir-486-5p, hsa-mir-451, and hsa-mir-92a were up-regulated and hsa-mir-30a, hsa-mir-382, and hsa-mir-136 were down-regulated in bromocriptine-resistant prolactinomas in comparison with bromocriptine-sensitive prolactinomas.
Key Molecule: hsa-miR-142-3p [2]
Resistant Disease Prolactin-secreting adenoma [ICD-11: 2F37.Y]
Molecule Alteration Expression
Up-regulation
Resistant Drug Bromocriptine
Experimental Note Identified from the Human Clinical Data
In Vitro Model KHM-5M cells Pleural effusion Homo sapiens (Human) CVCL_2975
Experiment for
Molecule Alteration
Solexa sequencing assay; qRT-PCR
Experiment for
Drug Resistance
Clinical diagnostic evaluation
Mechanism Description Hsa-mir-93, hsa-mir-17, hsa-mir-22*, hsa-mir-126*, hsa-mir-142-3p, hsa-mir-144*, hsa-mir-486-5p, hsa-mir-451, and hsa-mir-92a were up-regulated and hsa-mir-30a, hsa-mir-382, and hsa-mir-136 were down-regulated in bromocriptine-resistant prolactinomas in comparison with bromocriptine-sensitive prolactinomas.
Key Molecule: hsa-mir-144 [2]
Resistant Disease Prolactin-secreting adenoma [ICD-11: 2F37.Y]
Molecule Alteration Expression
Up-regulation
Resistant Drug Bromocriptine
Experimental Note Identified from the Human Clinical Data
In Vitro Model KHM-5M cells Pleural effusion Homo sapiens (Human) CVCL_2975
Experiment for
Molecule Alteration
Solexa sequencing assay; qRT-PCR
Experiment for
Drug Resistance
Clinical diagnostic evaluation
Mechanism Description Hsa-mir-93, hsa-mir-17, hsa-mir-22*, hsa-mir-126*, hsa-mir-142-3p, hsa-mir-144*, hsa-mir-486-5p, hsa-mir-451, and hsa-mir-92a were up-regulated and hsa-mir-30a, hsa-mir-382, and hsa-mir-136 were down-regulated in bromocriptine-resistant prolactinomas in comparison with bromocriptine-sensitive prolactinomas.
Key Molecule: hsa-mir-17 [2]
Resistant Disease Prolactin-secreting adenoma [ICD-11: 2F37.Y]
Molecule Alteration Expression
Up-regulation
Resistant Drug Bromocriptine
Experimental Note Identified from the Human Clinical Data
In Vitro Model KHM-5M cells Pleural effusion Homo sapiens (Human) CVCL_2975
Experiment for
Molecule Alteration
Solexa sequencing assay; qRT-PCR
Experiment for
Drug Resistance
Clinical diagnostic evaluation
Mechanism Description Hsa-mir-93, hsa-mir-17, hsa-mir-22*, hsa-mir-126*, hsa-mir-142-3p, hsa-mir-144*, hsa-mir-486-5p, hsa-mir-451, and hsa-mir-92a were up-regulated and hsa-mir-30a, hsa-mir-382, and hsa-mir-136 were down-regulated in bromocriptine-resistant prolactinomas in comparison with bromocriptine-sensitive prolactinomas.
Key Molecule: hsa-mir-22 [2]
Resistant Disease Prolactin-secreting adenoma [ICD-11: 2F37.Y]
Molecule Alteration Expression
Up-regulation
Resistant Drug Bromocriptine
Experimental Note Identified from the Human Clinical Data
In Vitro Model KHM-5M cells Pleural effusion Homo sapiens (Human) CVCL_2975
Experiment for
Molecule Alteration
Solexa sequencing assay; qRT-PCR
Experiment for
Drug Resistance
Clinical diagnostic evaluation
Mechanism Description Hsa-mir-93, hsa-mir-17, hsa-mir-22*, hsa-mir-126*, hsa-mir-142-3p, hsa-mir-144*, hsa-mir-486-5p, hsa-mir-451, and hsa-mir-92a were up-regulated and hsa-mir-30a, hsa-mir-382, and hsa-mir-136 were down-regulated in bromocriptine-resistant prolactinomas in comparison with bromocriptine-sensitive prolactinomas.
Key Molecule: hsa-mir-30a [2]
Resistant Disease Prolactin-secreting adenoma [ICD-11: 2F37.Y]
Molecule Alteration Expression
Down-regulation
Resistant Drug Bromocriptine
Experimental Note Identified from the Human Clinical Data
In Vitro Model KHM-5M cells Pleural effusion Homo sapiens (Human) CVCL_2975
Experiment for
Molecule Alteration
Solexa sequencing assay; qRT-PCR
Experiment for
Drug Resistance
Clinical diagnostic evaluation
Mechanism Description Hsa-mir-93, hsa-mir-17, hsa-mir-22*, hsa-mir-126*, hsa-mir-142-3p, hsa-mir-144*, hsa-mir-486-5p, hsa-mir-451, and hsa-mir-92a were up-regulated and hsa-mir-30a, hsa-mir-382, and hsa-mir-136 were down-regulated in bromocriptine-resistant prolactinomas in comparison with bromocriptine-sensitive prolactinomas.
Key Molecule: hsa-mir-382 [2]
Resistant Disease Prolactin-secreting adenoma [ICD-11: 2F37.Y]
Molecule Alteration Expression
Down-regulation
Resistant Drug Bromocriptine
Experimental Note Identified from the Human Clinical Data
In Vitro Model KHM-5M cells Pleural effusion Homo sapiens (Human) CVCL_2975
Experiment for
Molecule Alteration
Solexa sequencing assay; qRT-PCR
Experiment for
Drug Resistance
Clinical diagnostic evaluation
Mechanism Description Hsa-mir-93, hsa-mir-17, hsa-mir-22*, hsa-mir-126*, hsa-mir-142-3p, hsa-mir-144*, hsa-mir-486-5p, hsa-mir-451, and hsa-mir-92a were up-regulated and hsa-mir-30a, hsa-mir-382, and hsa-mir-136 were down-regulated in bromocriptine-resistant prolactinomas in comparison with bromocriptine-sensitive prolactinomas.
Key Molecule: hsa-mir-451 [2]
Resistant Disease Prolactin-secreting adenoma [ICD-11: 2F37.Y]
Molecule Alteration Expression
Up-regulation
Resistant Drug Bromocriptine
Experimental Note Identified from the Human Clinical Data
In Vitro Model KHM-5M cells Pleural effusion Homo sapiens (Human) CVCL_2975
Experiment for
Molecule Alteration
Solexa sequencing assay; qRT-PCR
Experiment for
Drug Resistance
Clinical diagnostic evaluation
Mechanism Description Hsa-mir-93, hsa-mir-17, hsa-mir-22*, hsa-mir-126*, hsa-mir-142-3p, hsa-mir-144*, hsa-mir-486-5p, hsa-mir-451, and hsa-mir-92a were up-regulated and hsa-mir-30a, hsa-mir-382, and hsa-mir-136 were down-regulated in bromocriptine-resistant prolactinomas in comparison with bromocriptine-sensitive prolactinomas.
Key Molecule: hsa-miR-486-5p [2]
Resistant Disease Prolactin-secreting adenoma [ICD-11: 2F37.Y]
Molecule Alteration Expression
Up-regulation
Resistant Drug Bromocriptine
Experimental Note Identified from the Human Clinical Data
In Vitro Model KHM-5M cells Pleural effusion Homo sapiens (Human) CVCL_2975
Experiment for
Molecule Alteration
Solexa sequencing assay; qRT-PCR
Experiment for
Drug Resistance
Clinical diagnostic evaluation
Mechanism Description Hsa-mir-93, hsa-mir-17, hsa-mir-22*, hsa-mir-126*, hsa-mir-142-3p, hsa-mir-144*, hsa-mir-486-5p, hsa-mir-451, and hsa-mir-92a were up-regulated and hsa-mir-30a, hsa-mir-382, and hsa-mir-136 were down-regulated in bromocriptine-resistant prolactinomas in comparison with bromocriptine-sensitive prolactinomas.
Key Molecule: Long non-protein coding RNA (lnc886) [2]
Resistant Disease Prolactin-secreting adenoma [ICD-11: 2F37.Y]
Molecule Alteration Expression
Up-regulation
Resistant Drug Bromocriptine
Experimental Note Identified from the Human Clinical Data
In Vitro Model KHM-5M cells Pleural effusion Homo sapiens (Human) CVCL_2975
Experiment for
Molecule Alteration
Solexa sequencing assay; qRT-PCR
Experiment for
Drug Resistance
Clinical diagnostic evaluation
Mechanism Description Hsa-mir-93, hsa-mir-17, hsa-mir-22*, hsa-mir-126*, hsa-mir-142-3p, hsa-mir-144*, hsa-mir-486-5p, hsa-mir-451, and hsa-mir-92a were up-regulated and hsa-mir-30a, hsa-mir-382, and hsa-mir-136 were down-regulated in bromocriptine-resistant prolactinomas in comparison with bromocriptine-sensitive prolactinomas.
Key Molecule: hsa-mir-93 [2]
Resistant Disease Prolactin-secreting adenoma [ICD-11: 2F37.Y]
Molecule Alteration Expression
Up-regulation
Resistant Drug Bromocriptine
Experimental Note Identified from the Human Clinical Data
In Vitro Model C4-2 cells Prostate Homo sapiens (Human) CVCL_4782
KHM-5M cells Pleural effusion Homo sapiens (Human) CVCL_2975
Experiment for
Drug Resistance
Clinical diagnostic evaluation
Mechanism Description Hsa-mir-93, hsa-mir-17, hsa-mir-22*, hsa-mir-126*, hsa-mir-142-3p, hsa-mir-144*, hsa-mir-486-5p, hsa-mir-451, and hsa-mir-92a were up-regulated and hsa-mir-30a, hsa-mir-382, and hsa-mir-136 were down-regulated in bromocriptine-resistant prolactinomas in comparison with bromocriptine-sensitive prolactinomas.
       Regulation by the Disease Microenvironment (RTDM) Click to Show/Hide
Key Molecule: Mothers against decapentaplegic homolog 3 (SMAD3) [3]
Resistant Disease Prolactinomas [ICD-11: 2F37.2]
Molecule Alteration Expression
Up-regulation
Resistant Drug Bromocriptine
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation TGF-beta 1/Smad3 pathway Activation hsa04350
In Vitro Model HS27 cells Bone Homo sapiens (Human) CVCL_0E34
MMQ cells Pituitary gland Rattus norvegicus (Rat) CVCL_2117
Experiment for
Molecule Alteration
Western blotting assay
Experiment for
Drug Resistance
CCK8 assay
Mechanism Description TGF-beta1 promotes the synthesis and secretion of collagen fibers in fibroblasts and that the TGF-beta1/Smad3 pathway is involved in the mechanism of prolactinoma resistance by increasing fibrosis through interactions with fibroblasts.
Key Molecule: Mothers against decapentaplegic homolog 4 (SMAD4) [3]
Resistant Disease Prolactinomas [ICD-11: 2F37.2]
Molecule Alteration Expression
Up-regulation
Resistant Drug Bromocriptine
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation TGF-beta 1/Smad3 pathway Activation hsa04350
In Vitro Model HS27 cells Bone Homo sapiens (Human) CVCL_0E34
MMQ cells Pituitary gland Rattus norvegicus (Rat) CVCL_2117
Experiment for
Molecule Alteration
Western blotting assay
Experiment for
Drug Resistance
CCK8 assay
Mechanism Description TGF-beta1 promotes the synthesis and secretion of collagen fibers in fibroblasts and that the TGF-beta1/Smad3 pathway is involved in the mechanism of prolactinoma resistance by increasing fibrosis through interactions with fibroblasts.
Key Molecule: TSPY like 2 (TSPYL2) [3]
Resistant Disease Prolactinomas [ICD-11: 2F37.2]
Molecule Alteration Expression
Up-regulation
Resistant Drug Bromocriptine
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation TGF-beta 1/Smad3 pathway Activation hsa04350
In Vitro Model HS27 cells Bone Homo sapiens (Human) CVCL_0E34
MMQ cells Pituitary gland Rattus norvegicus (Rat) CVCL_2117
Experiment for
Molecule Alteration
Western blotting assay
Experiment for
Drug Resistance
CCK8 assay
Mechanism Description TGF-beta1 promotes the synthesis and secretion of collagen fibers in fibroblasts and that the TGF-beta1/Smad3 pathway is involved in the mechanism of prolactinoma resistance by increasing fibrosis through interactions with fibroblasts.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Cyclin-dependent kinase inhibitor 1A (CDKN1A) [2]
Resistant Disease Prolactin-secreting adenoma [ICD-11: 2F37.Y]
Molecule Alteration Expression
Down-regulation
Resistant Drug Bromocriptine
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell invasion Activation hsa05200
Cell migration Activation hsa04670
In Vitro Model C4-2 cells Prostate Homo sapiens (Human) CVCL_4782
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
CCK-8 assay
Mechanism Description Knockdown of mir-93 increased the sensitivity of MMQ cells to bromocriptine treatment, and these effects were abolished when p21 was knocked-down using siRNA.
Cabergoline
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Dopamine receptor D2 (DRD2) [1]
Resistant Disease Prolactin-secreting adenoma [ICD-11: 2F37.Y]
Molecule Alteration Expression
Down-regulation
Resistant Drug Cabergoline
Experimental Note Identified from the Human Clinical Data
Mechanism Description Generally, the effectiveness of BRC or CAB has been related to a decreased expression in DRs, as the expression of such receptors has been shown to correlate with responsiveness to therapy in lactotroph, somatotroph, corticotroph and in clinically nonfunctioning PitNET.
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: hsa-miR-17-5p [2]
Resistant Disease Prolactin-secreting adenoma [ICD-11: 2F37.Y]
Molecule Alteration Expression
Up-regulation
Resistant Drug Cabergoline
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell proliferation Activation hsa05200
In Vitro Model C4-2 cells Prostate Homo sapiens (Human) CVCL_4782
Experiment for
Molecule Alteration
Solexa sequencing assay; qRT-PCR
Experiment for
Drug Resistance
CCK-8 assay
Mechanism Description Overexpression of mir-93 increased resistance to bromocriptine and cabergoline treatment.
Key Molecule: hsa-mir-93 [2]
Resistant Disease Prolactin-secreting adenoma [ICD-11: 2F37.Y]
Molecule Alteration Expression
Up-regulation
Resistant Drug Cabergoline
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell proliferation Activation hsa05200
In Vitro Model C4-2 cells Prostate Homo sapiens (Human) CVCL_4782
Experiment for
Molecule Alteration
Solexa sequencing assay; qRT-PCR
Experiment for
Drug Resistance
CCK-8 assay
Mechanism Description Overexpression of mir-93 increased resistance to bromocriptine and cabergoline treatment.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Cyclin-dependent kinase inhibitor 1A (CDKN1A) [2]
Resistant Disease Prolactin-secreting adenoma [ICD-11: 2F37.Y]
Molecule Alteration Expression
Down-regulation
Resistant Drug Cabergoline
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell proliferation Activation hsa05200
In Vitro Model C4-2 cells Prostate Homo sapiens (Human) CVCL_4782
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
CCK-8 assay
Mechanism Description Knockdown of mir-93 increased the sensitivity of MMQ cells to bromocriptine treatment, and these effects were abolished when p21 was knocked-down using siRNA.
Carboplatin
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Bcl-2-associated agonist of cell death (BAD) [4]
Resistant Disease Pituitary adenoma [ICD-11: 2F37.1]
Molecule Alteration Expression
Up-regulation
Resistant Drug Carboplatin
Experimental Note Identified from the Human Clinical Data
In Vitro Model Pituitary tumour stem-like cells Pituitary Homo sapiens (Human) N.A.
In Vivo Model NOD/SCID mice xenograft model Mus musculus
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
WST-1 proliferation assay
Mechanism Description Stem cells are generally known to preferentially express antiapoptotic genes, such as BCL-2, cIAP1, NAIP, and XIAP.The expression levels of these antiapoptotic genes in PASC1 were one- to sixfolds higher than those in its daughter cells.
Key Molecule: Baculoviral IAP repeat containing 2 (BIRC2) [4]
Resistant Disease Pituitary adenoma [ICD-11: 2F37.1]
Molecule Alteration Expression
Up-regulation
Resistant Drug Carboplatin
Experimental Note Identified from the Human Clinical Data
In Vitro Model Pituitary tumour stem-like cells Pituitary Homo sapiens (Human) N.A.
In Vivo Model NOD/SCID mice xenograft model Mus musculus
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
WST-1 proliferation assay
Mechanism Description Stem cells are generally known to preferentially express antiapoptotic genes, such as BCL-2, cIAP1, NAIP, and XIAP.The expression levels of these antiapoptotic genes in PASC1 were one- to sixfolds higher than those in its daughter cells.
Key Molecule: Baculoviral IAP repeat-containing protein 1 (BIRC1) [4]
Resistant Disease Pituitary adenoma [ICD-11: 2F37.1]
Molecule Alteration Expression
Up-regulation
Resistant Drug Carboplatin
Experimental Note Identified from the Human Clinical Data
In Vitro Model Pituitary tumour stem-like cells Pituitary Homo sapiens (Human) N.A.
In Vivo Model NOD/SCID mice xenograft model Mus musculus
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
WST-1 proliferation assay
Mechanism Description Stem cells are generally known to preferentially express antiapoptotic genes, such as BCL-2, cIAP1, NAIP, and XIAP.The expression levels of these antiapoptotic genes in PASC1 were one- to sixfolds higher than those in its daughter cells.
Key Molecule: E3 ubiquitin-protein ligase XIAP (XIAP) [4]
Resistant Disease Pituitary adenoma [ICD-11: 2F37.1]
Molecule Alteration Expression
Up-regulation
Resistant Drug Carboplatin
Experimental Note Identified from the Human Clinical Data
In Vitro Model Pituitary tumour stem-like cells Pituitary Homo sapiens (Human) N.A.
In Vivo Model NOD/SCID mice xenograft model Mus musculus
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
WST-1 proliferation assay
Mechanism Description Stem cells are generally known to preferentially express antiapoptotic genes, such as BCL-2, cIAP1, NAIP, and XIAP.The expression levels of these antiapoptotic genes in PASC1 were one- to sixfolds higher than those in its daughter cells.
Colchicine
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Irregularity in Drug Uptake and Drug Efflux (IDUE) Click to Show/Hide
Key Molecule: Multidrug resistance protein 1 (ABCB1) [5]
Resistant Disease Pituitary adenoma [ICD-11: 2F37.1]
Molecule Alteration Expression
Up-regulation
Resistant Drug Colchicine
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model GH4C1 cells Pituitary gland Rattus norvegicus (Rat) CVCL_0276
Experiment for
Molecule Alteration
Immunocytochemical staining assay
Experiment for
Drug Resistance
Lowry assay; Bradford assay
Mechanism Description Cells resistant to colchicine at 0.4 micrograms/ml, termed GH4C1/RC.4, exhibited the multidrug-resistance phenotype, as the LD50 values for colchicine, puromycin, actinomycin D, and doxorubicin were between 8 and 30 times greater than the corresponding values for the parental GH4C1 cells.Immunocytochemical staining with a monoclonal antibody, C219, to the 170-kilodalton P-glycoprotein showed directly that GH4C1/RC.4 cells overexpress P-glycoprotein.
Doxorubicin
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Irregularity in Drug Uptake and Drug Efflux (IDUE) Click to Show/Hide
Key Molecule: Multidrug resistance protein 1 (ABCB1) [5]
Resistant Disease Pituitary adenoma [ICD-11: 2F37.1]
Molecule Alteration Expression
Up-regulation
Resistant Drug Doxorubicin
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model GH4C1 cells Pituitary gland Rattus norvegicus (Rat) CVCL_0276
Experiment for
Molecule Alteration
Immunocytochemical staining assay
Experiment for
Drug Resistance
Lowry assay; Bradford assay
Mechanism Description Cells resistant to colchicine at 0.4 micrograms/ml, termed GH4C1/RC.4, exhibited the multidrug-resistance phenotype, as the LD50 values for colchicine, puromycin, actinomycin D, and doxorubicin were between 8 and 30 times greater than the corresponding values for the parental GH4C1 cells.Immunocytochemical staining with a monoclonal antibody, C219, to the 170-kilodalton P-glycoprotein showed directly that GH4C1/RC.4 cells overexpress P-glycoprotein.
Etoposide
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Bcl-2-associated agonist of cell death (BAD) [4]
Resistant Disease Pituitary adenoma [ICD-11: 2F37.1]
Molecule Alteration Expression
Up-regulation
Resistant Drug Etoposide
Experimental Note Identified from the Human Clinical Data
In Vitro Model Pituitary tumour stem-like cells Pituitary Homo sapiens (Human) N.A.
In Vivo Model NOD/SCID mice xenograft model Mus musculus
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
WST-1 proliferation assay
Mechanism Description Stem cells are generally known to preferentially express antiapoptotic genes, such as BCL-2, cIAP1, NAIP, and XIAP.The expression levels of these antiapoptotic genes in PASC1 were one- to sixfolds higher than those in its daughter cells.
Key Molecule: Baculoviral IAP repeat containing 2 (BIRC2) [4]
Resistant Disease Pituitary adenoma [ICD-11: 2F37.1]
Molecule Alteration Expression
Up-regulation
Resistant Drug Etoposide
Experimental Note Identified from the Human Clinical Data
In Vitro Model Pituitary tumour stem-like cells Pituitary Homo sapiens (Human) N.A.
In Vivo Model NOD/SCID mice xenograft model Mus musculus
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
WST-1 proliferation assay
Mechanism Description Stem cells are generally known to preferentially express antiapoptotic genes, such as BCL-2, cIAP1, NAIP, and XIAP.The expression levels of these antiapoptotic genes in PASC1 were one- to sixfolds higher than those in its daughter cells.
Key Molecule: Baculoviral IAP repeat-containing protein 1 (BIRC1) [4]
Resistant Disease Pituitary adenoma [ICD-11: 2F37.1]
Molecule Alteration Expression
Up-regulation
Resistant Drug Etoposide
Experimental Note Identified from the Human Clinical Data
In Vitro Model Pituitary tumour stem-like cells Pituitary Homo sapiens (Human) N.A.
In Vivo Model NOD/SCID mice xenograft model Mus musculus
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
WST-1 proliferation assay
Mechanism Description Stem cells are generally known to preferentially express antiapoptotic genes, such as BCL-2, cIAP1, NAIP, and XIAP.The expression levels of these antiapoptotic genes in PASC1 were one- to sixfolds higher than those in its daughter cells.
Key Molecule: E3 ubiquitin-protein ligase XIAP (XIAP) [4]
Resistant Disease Pituitary adenoma [ICD-11: 2F37.1]
Molecule Alteration Expression
Up-regulation
Resistant Drug Etoposide
Experimental Note Identified from the Human Clinical Data
In Vitro Model Pituitary tumour stem-like cells Pituitary Homo sapiens (Human) N.A.
In Vivo Model NOD/SCID mice xenograft model Mus musculus
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
WST-1 proliferation assay
Mechanism Description Stem cells are generally known to preferentially express antiapoptotic genes, such as BCL-2, cIAP1, NAIP, and XIAP.The expression levels of these antiapoptotic genes in PASC1 were one- to sixfolds higher than those in its daughter cells.
Octreotide
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: Forkhead box protein O3 (FOXO3) [6]
Resistant Disease Pituitary adenoma [ICD-11: 2F37.1]
Molecule Alteration Expression
Up-regulation
Resistant Drug Octreotide
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
In Vitro Model HCT8 cells Colon Homo sapiens (Human) CVCL_2478
LN-18 cells Brain Homo sapiens (Human) CVCL_0392
ATCC 293T cells Fetal kidney Homo sapiens (Human) CVCL_0063
SH-1-V3 cells Esophagus Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
WST-1 assay
Mechanism Description miR-34a upregulation leads not only to increased cell proliferation and GH secretion in vitro, but also induces resistance to the antiproliferative and hormonal effects of the first-generation somatostatin analog, octreotide.
Temozolomide
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: DNA mismatch repair protein Msh6 (MSH6) [7]
Resistant Disease Pituitary cancer [ICD-11: 2F37.0]
Molecule Alteration Structural variation
Copy number loss
Resistant Drug Temozolomide
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Low throughput experiment assay
Mechanism Description Loss of MSH6 occurred during the progression from an atypical prolactinoma to a pituitary carcinoma, which may have caused resistance to TMZ treatment.
Investigative Drug(s)
2 drug(s) in total
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Actinomycin D
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Irregularity in Drug Uptake and Drug Efflux (IDUE) Click to Show/Hide
Key Molecule: Multidrug resistance protein 1 (ABCB1) [5]
Resistant Disease Pituitary adenoma [ICD-11: 2F37.1]
Molecule Alteration Expression
Up-regulation
Resistant Drug Actinomycin D
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model GH4C1 cells Pituitary gland Rattus norvegicus (Rat) CVCL_0276
Experiment for
Molecule Alteration
Immunocytochemical staining assay
Experiment for
Drug Resistance
Lowry assay; Bradford assay
Mechanism Description Cells resistant to colchicine at 0.4 micrograms/ml, termed GH4C1/RC.4, exhibited the multidrug-resistance phenotype, as the LD50 values for colchicine, puromycin, actinomycin D, and doxorubicin were between 8 and 30 times greater than the corresponding values for the parental GH4C1 cells.Immunocytochemical staining with a monoclonal antibody, C219, to the 170-kilodalton P-glycoprotein showed directly that GH4C1/RC.4 cells overexpress P-glycoprotein.
Puromycin
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Irregularity in Drug Uptake and Drug Efflux (IDUE) Click to Show/Hide
Key Molecule: Multidrug resistance protein 1 (ABCB1) [5]
Resistant Disease Pituitary adenoma [ICD-11: 2F37.1]
Molecule Alteration Expression
Up-regulation
Resistant Drug Puromycin
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model GH4C1 cells Pituitary gland Rattus norvegicus (Rat) CVCL_0276
Experiment for
Molecule Alteration
Immunocytochemical staining assay
Experiment for
Drug Resistance
Lowry assay; Bradford assay
Mechanism Description Cells resistant to colchicine at 0.4 micrograms/ml, termed GH4C1/RC.4, exhibited the multidrug-resistance phenotype, as the LD50 values for colchicine, puromycin, actinomycin D, and doxorubicin were between 8 and 30 times greater than the corresponding values for the parental GH4C1 cells.Immunocytochemical staining with a monoclonal antibody, C219, to the 170-kilodalton P-glycoprotein showed directly that GH4C1/RC.4 cells overexpress P-glycoprotein.
References
Ref 1 Resistance to Dopamine Agonists in Pituitary Tumors: Molecular Mechanisms .Front Endocrinol (Lausanne). 2022 Jan 12;12:791633. doi: 10.3389/fendo.2021.791633. eCollection 2021. 10.3389/fendo.2021.791633
Ref 2 MicroRNA expression profile of bromocriptine-resistant prolactinomas .Mol Cell Endocrinol. 2014 Sep;395(1-2):10-8. doi: 10.1016/j.mce.2014.07.014. Epub 2014 Jul 23. 10.1016/j.mce.2014.07.014
Ref 3 Role of TGF-Beta1/Smad3-mediated fibrosis in drug resistance mechanism of prolactinoma .Brain Res. 2018 Nov 1;1698:204-212. doi: 10.1016/j.brainres.2018.07.024. Epub 2018 Jul 27. 10.1016/j.brainres.2018.07.024
Ref 4 Isolation of tumour stem-like cells from benign tumours .Br J Cancer. 2009 Jul 21;101(2):303-11. doi: 10.1038/sj.bjc.6605142. Epub 2009 Jun 30. 10.1038/sj.bjc.6605142
Ref 5 Characterization of multidrug-resistant pituitary tumor cells .Endocrinology. 1992 Jun;130(6):3246-56. doi: 10.1210/endo.130.6.1350759. 10.1210/endo.130.6.1350759
Ref 6 miR-34a is upregulated in AIP-mutated somatotropinomas and promotes octreotide resistance .Int J Cancer. 2020 Dec 15;147(12):3523-3538. doi: 10.1002/ijc.33268. Epub 2020 Sep 10. 10.1002/ijc.33268
Ref 7 A mechanism of acquiring temozolomide resistance during transformation of atypical prolactinoma into prolactin-producing pituitary carcinoma: case report. Neurosurgery. 2011 Jun;68(6):E1761-7; discussion E1767. doi: 10.1227/NEU.0b013e318217161a.

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