ArticlePloS one2012
Differential regulation of breast cancer-associated genes by progesterone receptor isoforms PRA and PRB in a new bi-inducible breast cancer cell line.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 45 citations in OpenAlex.
- Effects of the Overexpression of Progesterone Receptors on a Precancer p53 and Rb-Defective Human Fallopian Tube Epithelial Cell Line.International journal of molecular sciences · 2023Article
- Role of Transcription Factors in the Management of Preterm Birth: Impact on Future Treatment Strategies.Reproductive sciences (Thousand Oaks, Calif.) · 2023Review
- Choosing the right partner in hormone-dependent gene regulation: Glucocorticoid and progesterone receptors crosstalk in breast cancer cells.Frontiers in endocrinology · 2022Review
- 27-Hydroxycholesterol, The Estrogen Receptor Modulator, Alters DNA Methylation in Breast Cancer.Frontiers in endocrinology · 2022Article
- Steroid Receptors in Breast Cancer: Understanding of Molecular Function as a Basis for Effective Therapy Development.Cancers · 2021Review
- Lost but Not Least-Novel Insights into Progesterone Receptor Loss in Estrogen Receptor-Positive Breast Cancer.Cancers · 2021Review
- Crosstalk between progesterone receptor membrane component 1 and estrogen receptor α promotes breast cancer cell proliferation.Laboratory investigation; a journal of technical methods and pathology · 2021Article
- Article
- Review
- 90 YEARS OF PROGESTERONE: Molecular mechanisms of progesterone receptor action on the breast cancer genome.Journal of molecular endocrinology · 2020Review
- Biomarkers for Pancreatic Neuroendocrine Neoplasms (PanNENs) Management-An Updated Review.Frontiers in oncology · 2020Review
- Differential expression of progesterone receptor isoforms related toInternational journal of reproductive biomedicine · 2019Article
- Cadmium induces progesterone receptor gene expression via activation of estrogen receptor in human ovarian cancer cells.Research in pharmaceutical sciences · 2018Article
- Gene expression profile and cancer-associated pathways linked to progesterone receptor isoform a (PRA) predominance in transgenic mouse mammary glands.BMC cancer · 2018Article
- Progesterone receptor isoforms, agonists and antagonists differentially reprogram estrogen signaling.Oncotarget · 2018Article
- Isoform specificity of progesterone receptor antibodies.The journal of pathology. Clinical research · 2017Article
- Progesterone Receptor Isoform Ratio: A Breast Cancer Prognostic and Predictive Factor for Antiprogestin Responsiveness.Journal of the National Cancer Institute · 2017Article
- Steroid hormone receptors as prognostic markers in breast cancer.American journal of cancer research · 2017Review
- Progesterone Receptor Signaling in Uterine Myometrial Physiology and Preterm Birth.Current topics in developmental biology · 2017Review
- Anti-Tumoral Effects of Anti-Progestins in a Patient-Derived Breast Cancer Xenograft Model.Hormones & cancer · 2016Article
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Progesterone receptor isoforms (PRA and PRB) are expressed at equal levels in normal mammary cells. However, alteration in PRA/PRB expression is often observed in aggressive breast cancer suggesting differential contribution of PR isoforms in carcinogenesis. The mechanisms underlying such processes remain to be established mainly due to paucity of appropriate cellular models. To investigate the role of PR isoforms and the impact of imbalanced PRA/PRB ratio in transcriptional regulation, we have generated an original human breast cancer cell line conditionally expressing PRA and/or PRB in dose-dependence of non-steroid inducers. We first focused on PR-dependent transcriptional regulation of the paracrine growth factor gene amphiregulin (AREG) playing important role in cancer. Interestingly, unliganded PRA increases AREG expression, independently of estrogen receptor, yet inhibitable by antiprogestins. We show that functional outcome of epidermal growth factor (EGF) on such regulation is highly dependent on PRA/PRB ratio. Using this valuable model, genome-wide transcriptomic studies allowed us to determine the differential effects of PRA and PRB as a function of hormonal status. We identified a large number of novel PR-regulated genes notably implicated in breast cancer and metastasis and demonstrated that imbalanced PRA/PRB ratio strongly impact their expression predicting poor outcome in breast cancer. In sum, our unique cell-based system strongly suggests that PRA/PRB ratio is a critical determinant of PR target gene selectivity and responses to hormonal/growth factor stimuli. These findings provide molecular support for the aggressive phenotype of breast cancers with impaired expression of PRA or PRB.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.