ArticleBMC cancer2015
The unique transcriptional response produced by concurrent estrogen and progesterone treatment in breast cancer cells results in upregulation of growth factor pathways and switching from a Luminal A to a Basal-like subtype.
Article in BMC cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 38 citations in OpenAlex.
- Article
- Molecular characterization of breast cancer cell pools with normal or reduced ability to respond to progesterone: a study based on RNA-seq.Journal, genetic engineering & biotechnology · 2023Article
- Identification of Candidate Genes in Breast Cancer Induced by Estrogen Plus Progestogens Using Bioinformatic Analysis.International journal of molecular sciences · 2022Article
- ESR1 mutant breast cancers show elevated basal cytokeratins and immune activation.Nature communications · 2022Article
- Article
- Functional Significance of Selective Expression of ERα and ERβ in Mammary Gland Organ Culture.International journal of molecular sciences · 2021Article
- Postpartum breast cancer has a distinct molecular profile that predicts poor outcomes.Nature communications · 2021Article
- The antiandrogen enzalutamide downregulates TMPRSS2 and reduces cellular entry of SARS-CoV-2 in human lung cells.Nature communications · 2021Article
- Ovarian cycle stage critically affects 21-gene recurrence scores in Mmtv-Pymt mouse mammary tumours.BMC cancer · 2021Article
- Comparison of hormone-induced mRNA and protein biomarker expression changes in breast cancer cells.Breast cancer research and treatment · 2021Article
- How to Predict Metastasis in Luminal Breast Cancer? Current Solutions and Future Prospects.International journal of molecular sciences · 2020Review
- Timing of breast cancer surgery during the menstrual cycle-is there an optimal time of the month?Oncology letters · 2020Review
- Discordance in 21-gene recurrence scores between paired breast cancer samples is inversely associated with patient age.Breast cancer research : BCR · 2020Article
- 90 YEARS OF PROGESTERONE: Steroid receptors as MAPK signaling sensors in breast cancer: let the fates decide.Journal of molecular endocrinology · 2020Review
- 90 YEARS OF PROGESTERONE: Molecular mechanisms of progesterone receptor action on the breast cancer genome.Journal of molecular endocrinology · 2020Review
- Up-regulation of the kinase geneThe Journal of biological chemistry · 2018Article
- Deciphering Steroid Receptor Crosstalk in Hormone-Driven Cancers.Endocrinology · 2018Review
- Knockdown of miR-194-5p inhibits cell proliferation, migration and invasion in breast cancer by regulating the Wnt/β-catenin signaling pathway.International journal of molecular medicine · 2018Article
- Cancer Stem Cell Phenotypes in ERMolecular cancer research : MCR · 2018Article
- Novel Androgen Receptor Coregulator GRHL2 Exerts Both Oncogenic and Antimetastatic Functions in Prostate Cancer.Cancer research · 2017Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIn breast cancer, progesterone receptor (PR) positivity or abundance is positively associated with survival and treatment response. It was initially believed that PR was a useful diagnostic marker of estrogen receptor activity, but increasingly PR has been recognised to play an important biological role in breast homeostasis, carcinogenesis and metastasis. Although PR expression is almost exclusively observed in estrogen receptor positive tumors, few studies have investigated the cellular mechanisms of PR action in the context of ongoing estrogen signalling.
methodsIn this study, we contrast PR function in estrogen pretreated ZR-75-1 breast cancer cells with vehicle treated ZR-75-1 and T-47D breast cancer cells using expression microarrays and chromatin immunoprecipitation-sequencing.
resultsEstrogen cotreatment caused a dramatic increase in the number of genes regulated by progesterone in ZR-75-1 cells. In T-47D cells that have naturally high levels of PR, estrogen and progesterone cotreatment resulted in a reduction in the number of regulated genes in comparison to treatment with either hormone alone. At a genome level, estrogen pretreatment of ZR-75-1 cells led to a 10-fold increase in the number of PR DNA binding sites detected using ChIP-sequencing. Time course assessment of progesterone regulated genes in the context of estrogen pretreatment highlighted a series of important regulatory pathways, including those driven by epithelial growth factor receptor (EGFR). Importantly, progesterone applied to cells pretreated with estradiol resulted in switching of the PAM50-determined intrinsic breast cancer subtype from Luminal A to Basal-like, and increased the Oncotype DX® Unscaled Recurrence Score.
conclusionEstrogen pretreatment of breast cancer cells increases PR steady state levels, resulting in an unequivocal progesterone response that upregulates key members of growth factor pathways. The transformative changes progesterone exerts on the breast cancer subtype suggest that these subtyping tools should be used with caution in premenopausal women.
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