Split Decisions in Hormone Signaling: Distinct Roles for Progesterone Receptor Isoforms in Breast Cancer Biology.

IF 3.3 3区医学 Q2 ENDOCRINOLOGY & METABOLISM

Endocrinology Pub Date : 2025-10-23 DOI:10.1210/endocr/bqaf155

Noelle E Gillis, Susan I Schmidt, Carol A Lange

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Abstract

The progesterone receptor (PR) is a critical regulator of hormone signaling in breast tissue, with its two primary isoforms, PR-A and PR-B, exhibiting distinct and sometimes opposing functions. These isoforms arise from alternative promoter usage within the PGR gene, resulting in structural differences that influence their transcriptional activity, regulatory interactions, and post-translational modifications. While PR-B is a potent transcriptional activator, PR-A can act as a dominant repressor, modulating the activity of PR-B, estrogen receptor-alpha (ER), and other nuclear receptors. This review explores the historical discovery of PR isoforms, their structural and functional differences, and the molecular mechanisms governing their transcriptional regulation. We also discuss their physiological roles in normal mammary gland development and how their dysregulation contributes to breast cancer progression, endocrine resistance, and cancer stem cell expansion. Understanding the distinct roles of PR isoforms in breast cancer biology holds significant implications for developing targeted therapeutic strategies aimed at modulating isoform-specific PR activity in hormone-driven cancers.

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激素信号传导中的分裂决定：孕激素受体异构体在乳腺癌生物学中的独特作用。

孕激素受体（PR）是乳腺组织中激素信号的关键调节因子，其两个主要亚型PR- a和PR- b表现出不同的，有时相反的功能。这些同工型源于PGR基因中不同启动子的使用，导致影响其转录活性、调控相互作用和翻译后修饰的结构差异。虽然PR-B是一种有效的转录激活剂，PR-A可以作为一种显性抑制因子，调节PR-B、雌激素受体（ER）和其他核受体的活性。本文综述了PR亚型的历史发现，它们的结构和功能差异，以及调控它们转录调控的分子机制。我们还讨论了它们在正常乳腺发育中的生理作用，以及它们的失调如何促进乳腺癌的进展、内分泌抵抗和癌症干细胞的扩增。了解PR亚型在乳腺癌生物学中的独特作用，对于开发靶向治疗策略具有重要意义，这些策略旨在调节激素驱动型癌症中特异性PR亚型的活性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Endocrinology 医学-内分泌学与代谢

CiteScore

8.10

自引率

4.20%

发文量

195

审稿时长

2-3 weeks

期刊介绍： The mission of Endocrinology is to be the authoritative source of emerging hormone science and to disseminate that new knowledge to scientists, clinicians, and the public in a way that will enable "hormone science to health." Endocrinology welcomes the submission of original research investigating endocrine systems and diseases at all levels of biological organization, incorporating molecular mechanistic studies, such as hormone-receptor interactions, in all areas of endocrinology, as well as cross-disciplinary and integrative studies. The editors of Endocrinology encourage the submission of research in emerging areas not traditionally recognized as endocrinology or metabolism in addition to the following traditionally recognized fields: Adrenal; Bone Health and Osteoporosis; Cardiovascular Endocrinology; Diabetes; Endocrine-Disrupting Chemicals; Endocrine Neoplasia and Cancer; Growth; Neuroendocrinology; Nuclear Receptors and Their Ligands; Obesity; Reproductive Endocrinology; Signaling Pathways; and Thyroid.