Progesterone modulates cell growth via integrin αvβ3-dependent pathway in progesterone receptor-negative MDA-MB-231 cells.

Progesterone (P) plays a pivotal role in regulating the cancer progression of various types, including breast cancer, primarily through its interaction with the P receptor (PR). In PR-negative breast cancer cells, P appears to function in mediating cancer progression, such as cell growth. However, the mechanisms underlying the roles of P in PR-negative breast cancer cells remain incompletely understood. This study aimed to investigate the effects of P on cell proliferation, gene expression, and signal transduction in PR-negative MDA-MB-231 breast cancer cells. P-activated genes, associated with proliferation in breast cancer cells, exhibit a stimulating effect on cell growth in PR-negative MDA-MB-231 cells, while demonstrating an inhibitory impact in PR-positive MCF-7 cells. The use of arginine-glycine-aspartate (RGD) peptide successfully blocked P-induced extracellular signal-regulated kinase 1/2 (ERK1/2) activation, aligning with computational models of P binding to integrin αvβ3. Disrupting integrin αvβ3 binding with RGD peptide or anti-integrin αvβ3 antibody altered P-induced expression of proliferative genes and modified P-induced cell growth in breast cancer cells. In conclusion, integrin αvβ3 appears to mediate P-induced ERK1/2 signal pathway to regulate proliferation via alteration of proliferation-related gene expression in PR-negative breast cancer cells.