Regulation of progesterone receptor expression in endometriosis, endometrial cancer, and breast cancer by estrogen, polymorphisms, transcription factors, epigenetic alterations, and ubiquitin-proteasome system

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This paper explores the regulation of progesterone receptor expression in endometriosis, endometrial cancer, and breast cancer through estrogen, genetic variations, transcription factors, epigenetic changes, and the ubiquitin-proteasome system.

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Abstract

The uterus and breasts are hormone-responsive tissues. Progesterone and estradiol regulate gonadotropin secretion, prepare the endometrium for implantation, maintain pregnancy, and regulate the differentiation of breast tissue. Dysregulation of these hormones causes endometriosis, endometrial cancer, and breast cancer, damaging the physical and mental health of women. Emerging evidence has shown that progesterone resistance or elevated progesterone activity is the primary hormonal substrate of these diseases. Since progesterone acts through its specific nuclear receptor, the abnormal expression of the progesterone receptor (PR) dysregulates progesterone function. This review discusses the regulatory mechanisms of PR expression in patients with endometriosis, and endometrial or breast cancer, including estrogen, polymorphisms, transcription factors, epigenetics, and the ubiquitin-proteasome system. (1) Estrogen promotes the expression of PRA (a PR isoform) mRNA and protein through the interaction of estrogen receptors (ERs) and Sp1 with half-ERE/Sp1 binding sites. ERs also affect the binding of Sp1 and Sp1 sites to promote the expression of PRB (another PR isoform)(2) PR polymorphisms, mainly PROGINS and + 331 G/A polymorphism, regulate PR expression by affecting DNA methylation and transcription factor binding. (3) The influence of epigenetic alterations on PR expression occurs through DNA methylation, histone modification, and microRNA. (4) As one of the main protein degradation pathways in vivo, the ubiquitin-proteasome system (UPS) regulates PR expression by participating in protein degradation. These mechanisms may provide new molecular targets for diagnosing and treating endometriosis, endometrial, and breast cancer.

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Condition tags

endometriosis

MeSH descriptors

Breast Neoplasms Breast Neoplasms Breast Neoplasms Breast Neoplasms Breast Neoplasms Breast Neoplasms Breast Neoplasms Breast Neoplasms Breast Neoplasms Breast Neoplasms Breast Neoplasms Breast Neoplasms Breast Neoplasms Breast Neoplasms Breast Neoplasms Breast Neoplasms Breast Neoplasms Breast Neoplasms Breast Neoplasms Breast Neoplasms

Citation neighborhood

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europepmc
last seen: 2026-08-06T06:07:45.168820+00:00
openalex
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pubmed
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License: CC0 · commercial use OK