Molecule Information

General Information of the Molecule (ID: Mol01903)

• Name: Progesterone receptor (PGR) ,Homo sapiens
• Synonyms: PGR; NR3C3
• Molecule Type: Protein
• Gene Name: PGR
• Gene ID: 5241
• Location: chr11:101,029,624-101,129,813[-]
• Sequence:
  MTELKAKGPRAPHVAGGPPSPEVGSPLLCRPAAGPFPGSQTSDTLPEVSAIPISLDGLLF
  PRPCQGQDPSDEKTQDQQSLSDVEGAYSRAEATRGAGGSSSSPPEKDSGLLDSVLDTLLA
  PSGPGQSQPSPPACEVTSSWCLFGPELPEDPPAAPATQRVLSPLMSRSGCKVGDSSGTAA
  AHKVLPRGLSPARQLLLPASESPHWSGAPVKPSPQAAAVEVEEEDGSESEESAGPLLKGK
  PRALGGAAAGGGAAAVPPGAAAGGVALVPKEDSRFSAPRVALVEQDAPMAPGRSPLATTV
  MDFIHVPILPLNHALLAARTRQLLEDESYDGGAGAASAFAPPRSSPCASSTPVAVGDFPD
  CAYPPDAEPKDDAYPLYSDFQPPALKIKEEEEGAEASARSPRSYLVAGANPAAFPDFPLG
  PPPPLPPRATPSRPGEAAVTAAPASASVSSASSSGSTLECILYKAEGAPPQQGPFAPPPC
  KAPGASGCLLPRDGLPSTSASAAAAGAAPALYPALGLNGLPQLGYQAAVLKEGLPQVYPP
  YLNYLRPDSEASQSPQYSFESLPQKICLICGDEASGCHYGVLTCGSCKVFFKRAMEGQHN
  YLCAGRNDCIVDKIRRKNCPACRLRKCCQAGMVLGGRKFKKFNKVRVVRALDAVALPQPV
  GVPNESQALSQRFTFSPGQDIQLIPPLINLLMSIEPDVIYAGHDNTKPDTSSSLLTSLNQ
  LGERQLLSVVKWSKSLPGFRNLHIDDQITLIQYSWMSLMVFGLGWRSYKHVSGQMLYFAP
  DLILNEQRMKESSFYSLCLTMWQIPQEFVKLQVSQEEFLCMKVLLLLNTIPLEGLRSQTQ
  FEEMRSSYIRELIKAIGLRQKGVVSSSQRFYQLTKLLDNLHDLVKQLHLYCLNTFIQSRA
  LSVEFPEMMSEVIAAQLPKILAGMVKPLLFHKK
• 3D-structure: PDB ID: 3G8O; Classification: Transcription; Method: X-ray diffraction; Resolution: 1.90 Å
• Function: The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Depending on the isoform, progesterone receptor functions as transcriptional activator or repressor.
• Uniprot ID: PRGR_HUMAN
• Ensembl ID: ENSG00000082175
• HGNC ID: HGNC:8910

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  ADTT: Aberration of the Drug's Therapeutic Target

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 2 drug(s) in total

Fulvestrant

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Triple-negative breast cancer [ICD-11: 2C60.9] [1]

• Resistant Disease: Triple-negative breast cancer [ICD-11: 2C60.9]
• Resistant Drug: Fulvestrant
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: EGFR/HER2 signaling pathway; Regulation; N.A.
• In Vitro Model: MCF7 (Ful-R) cells; Breast; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: qRT-PCR
• Mechanism Description: In this study, we investigated the molecular mechanism underlying the loss of ER, FOXO3a, and induction of HER2 in fulvestrant-resistant breast cancer. Short-term fulvestrant treatment degraded ER proteins via the ubiquitin-proteasome degradation pathway in MCF7 cells. MCF7 cells turn into highly proliferative cells (fulvestrant-resistant cells: Ful-R) after long-term fulvestrant treatment. These cells exhibit markedly suppressed estrogen and progesterone receptor levels. The phosphorylation of EGFR, HER2, and ERK was induced in Ful-R, and these phosphorylation inhibitors suppressed cell proliferation in Ful-R.

Medroxyprogesterone

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Endometrial cancer [ICD-11: 2C76.1] [2]

• Resistant Disease: Endometrial cancer [ICD-11: 2C76.1]
• Resistant Drug: Medroxyprogesterone
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SR786 cells; Pleural effusion; Homo sapiens (Human); CVCL_1711
• In Vitro Model: IshikawaPR cells; Endometrium; Homo sapiens (Human); CVCL_2529
• Experiment for Molecule Alteration: RTPCR
• Mechanism Description: The presence of the progesterone receptor (PR) is the precondition for progesterone response and PR is a predictive marker for response of progesterone. Progesterone binds to its receptor PR-A and PR-B, subsequently inhibiting tumor growth and promoting tumor apoptosis by regulating downstream genes. Constant stimulation of progesterone reduced the expression of PGR and promoted the development of drug resistance. Thus, downregulation of PR especially PRB must be involved in progesterone resistance. However, the molecular mechanism of PGR dysfunction remains unclear.

References

• Ref 1: Loss of ERalpha involved-HER2 induction mediated by the FOXO3a signaling pathway in fulvestrant-resistant breast cancer. Biochem Biophys Res Commun. 2025 Jan;742:151056.
• Ref 2: Comprehensive bioinformatics analysis of acquired progesterone resistance in endometrial cancer cell line .J Transl Med. 2019 Feb 27;17(1):58. doi: 10.1186/s12967-019-1814-6. 10.1186/s12967-019-1814-6