Crosstalk between progesterone receptor membrane component 1 and estrogen receptor α promotes breast cancer cell proliferation
| Autor: | Kira Tiula, Alejandra Bencomo, Anthony Do, Animesh Chatterjee, Adriana Galvez, Rajkumar Lakshmanaswamy, Ramadevi Subramani, Servando Rivera, Diego A. Pedroza, Navya Rashiraj |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Estrogen receptor Breast Neoplasms Pathology and Forensic Medicine 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Cell surface receptor Cell Line Tumor Progesterone receptor medicine Humans Molecular Biology PGRMC1 Cell Proliferation Estradiol Chemistry Estrogen Receptor alpha Membrane Proteins Cell Biology 030104 developmental biology Nuclear receptor Selective estrogen receptor modulator 030220 oncology & carcinogenesis Cancer research Female Receptors Progesterone Tamoxifen medicine.drug |
| Zdroj: | Laboratory Investigation. 101:733-744 |
| ISSN: | 0023-6837 |
| DOI: | 10.1038/s41374-021-00594-6 |
| Popis: | Progesterone (P4) and estradiol (E2) have been shown to stimulate and regulate breast cancer proliferation via classical nuclear receptor signaling through progesterone receptor (PR) and estrogen receptor α (ERα), respectively. However, the basis of communication between PR/ERα and membrane receptors remains largely unknown. Here, we aim to identify classical and nonclassical endocrine signaling mechanisms that can alter cell proliferation through a possible crosstalk between PR, ERα, and progesterone receptor membrane component 1 (PGRMC1), a membrane receptor frequently observed in breast cancer cells. While P4 and E2 treatment increased cell proliferation of ER+/PR+/PGRMC1 overexpressing breast cancer cells, silencing ERα and PR or treatment with selective estrogen receptor modulator (SERM) tamoxifen, or (PR-antagonist) RU-486 decreased cell proliferation. All four treatments rapidly altered PGRMC1 mRNA levels and protein expression. Furthermore, P4 and E2 treatments rapidly activated EGFR a known interacting partner of PGRMC1 and its downstream signaling. Interestingly, downregulation of ERα by tamoxifen and ERα silencing decreased the expression levels of PGRMC1 with no repercussions to PR expression. Strikingly PGRMC1 silencing decreased ERα expression irrespective of PR. METABRIC and TCGA datasets further demonstrated that PGRMC1 expression was comparable to that of ERα in Luminal A and B breast cancers. Targeting of PR, ERα, and PGRMC1 confirmed that a crosstalk between classical and nonclassical signaling mechanisms exists in ER+ breast cancer cells that could enhance the growth of ER+/PR+/PGRMC1 overexpressing tumors. |
| Databáze: | OpenAIRE |
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