Abstract 114: Progesterone via integrin αvβ3 induces cell proliferation in PR-negative breast cancer cells

Abstract Background: Progesterone (P4) stimulates reproductive functions such as ovulation and the initiation and maintenance of pregnancy. P4 regulates biological activities via its nuclear receptor. However, it is not fully understood mechanisms involved in P4 functions in PR-negative cells. Anchor protein integrin αvβ3 plays a vital role in cancer growth and metastasis. Methods: We investigated the effect of P4 in PR-positive breast cancer MCF-7 cells and PR-negative breast cancer MDA-MB-231 cells. The protein and RNA expression changes induced by P4 were both analyzed in two cell lines. At the same time, the anti-integrin αvβ3 antibody and RGD peptide were employed for investigating the role of integrin αvβ3 in P4 regulation. Results: P4 inhibited the proliferation in MCF-7 cells but stimulated cell growth in MDA-MB-231 cells. In addition to ERK1/2 activation, P4 stimulated the phosphorylation at Y397 and Y925 in focal adhesion kinase (FAK), a vital kinase in integrin ανβ3 signal pathway that modulated by co-treatment with anti-integrin αvβ3 antibody or RGD peptide. P4 activated the gene expression of integrin ανβ3, CCND1, PCNA, and MMP-9 in MDA-MB-231 cells. P4 also induced PD-L1 and CCND1 accumulation. Conclusions: Progesterone via integrin αvβ3-mediated signal transduction regulates gene expression, cell proliferation, and migration in TNBC cells. It is the first time to demonstrate that P4 binds with the cell surface anchor protein, integrin αvβ3, to stimulate cancer cell proliferation in PR-negative breast cancer cells. Keywords: Progesterone, Progesterone receptor, Integrin αvβ3, Breast cancer, Cell proliferation Citation Format: Hung-Yun Lin, Tung-Yung Huang, Tung-Cheng Chang, Han-Yu Chen, Haw-Ming Huang, Sheng-Yang Lee, Zi-Lin Li, Hung-Ru Chu, Jacqueline Whang-Peng, Kuan Wang. Progesterone via integrin αvβ3 induces cell proliferation in PR-negative breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 114.