Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
The progesterone receptor (PR) is a steroid-responsive nuclear receptor with two isoforms: PR-A and PR-B. Disruption of PR-A:PR-B signaling is associated with breast cancer through interactions with oncogenic co-regulatory proteins (CoRs). However, molecular details of isoform-specific PR-CoR interactions remain poorly understood. Using structural mass spectrometry, we investigate the sequential binding mechanism of purified full-length PR and intact CoRs, steroid receptor coactivator 3 (SRC3) and p300, as complexes on target DNA. Our findings reveal selective CoR NR-box binding by PR and unique interaction surfaces between PR and CoRs during complex assembly, providing a structural basis for CoR sequential binding on PR. Antagonist-bound PR showed persistent CoR interactions, challenging the classical model of nuclear receptor activation and repression. Collectively, we offer a peptide-level perspective on the organization of the PR transcriptional complex and infer the mechanisms behind the interactions of these proteins, both in active and inactive conformations.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11398526 | PMC |
| http://dx.doi.org/10.1101/2024.09.06.611729 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Medical treatment of fibroids: FIGO best practice guidance.
Int J Gynaecol Obstet
September 2025
Department of Gynecology and Obstetrics, Justus Liebig University Giessen, Giessen, Germany.
Even though uterine fibroids are a widespread condition, the range of approved medical treatment options remains limited. In fact, only a few drugs are officially approved for the therapy of fibroids. In both the USA and the European Medicines Agency region, selected gonadotropin-releasing hormone (GnRH) antagonists have been approved for this indication.
View Article and Find Full Text PDFApplicability of Oncotype DX Testing in a Diverse Breast Cancer Population in Hawaii.
Breast J
September 2025
University of Hawai'i Cancer Center, Honolulu, Hawaii, USA.
The Oncotype DX test is standardly used for patients with early-stage, hormone-receptor-positive, HER2-negative breast cancers to determine the benefit from chemotherapy and the likelihood of distant recurrence. The relationship between Oncotype DX recurrence scores and race/ethnicity is still being studied. This retrospective study aims to evaluate the relationship between Oncotype DX recurrence scores, race/ethnicity, and clinicopathological factors and to support the applicability of the Oncotype DX test for a diverse breast cancer population of Hawaii.
View Article and Find Full Text PDFA Case Report of Synchronous Multicentric Breast Carcinoma With Biologically Discordant Phenotypes: Luminal A and Triple-Negative Subtypes.
Cureus
August 2025
Medicine, Academy of Silesia, Katowice, POL.
We present the case of a 45-year-old Caucasian woman diagnosed with synchronous bicentric breast cancer of differing molecular phenotypes in the same breast. The first tumor, an invasive ductal carcinoma (G1), was estrogen and progesterone receptor-positive and HER2-negative, with a low proliferative index (Ki67 10%). A second lesion, located in a different quadrant and appearing within weeks after biopsy, exhibited a triple-negative phenotype and a higher proliferative index (Ki67 30%).
View Article and Find Full Text PDFSparking malignancy: nicotine as a driver of stemness and metastasis in triple-negative breast cancer.
J Pathol
September 2025
Sidney Kimmel Comprehensive Cancer Center and Department of Oncology, Johns Hopkins University, Baltimore, MD, USA.
Triple-negative breast cancer (TNBC) lacks expression of estrogen receptor (ER), progesterone receptor (PR), and HER2, and remains one of the most aggressive and therapeutically challenging breast cancer subtypes, marked by early relapse, metastasis, and limited targeted treatment options. In a recent study published in The Journal of Pathology, Kuo et al provide compelling evidence that nicotine exposure, whether from tobacco smoke or e-cigarette vapor, drives TNBC progression by promoting stem-like and metastatic phenotypes. Integrating clinical datasets, patient tissues, cell lines, and in vivo models, the authors demonstrate that nicotine enhances tumor aggressiveness via coordinated upregulation of CHRNA9 and IGF1R.
View Article and Find Full Text PDFTreatment consequence and adverse events of cyclin-dependent kinase 4/6 inhibitors on patients with hormone receptor-positive, HER2-negative metastatic breast cancer: a systematic review and meta-analysis.
Ann Med
December 2025
Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Background: Although some studies have indicated that CDK4/6 inhibitors are beneficial for the progression-free survival (PFS) and overall survival (OS) in breast cancer, evidence regarding the assessment of clinical response remains insufficient. Therefore, this study aims not only to evaluate the efficacy and safety of CDK4/6 inhibitors combined with endocrine therapy in HR(+)/HER2(-) metastatic breast cancer, but also to analyze the objective response rate (ORR) and clinical benefit rate (CBR), providing comprehensive clinical outcome insights.
Materials And Methods: A literature search was performed in PubMed, Embase, Cochrane Library, and ClinicalTrials.