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

Autor: Chung-Che Tsai, Yung-Ning Yang, Kuan Wang, Yu-Chun E. Chen, Yi-Fong Chen, Jen-Chang Yang, Zi-Lin Li, Haw-Ming Huang, Jens Z. Pedersen, Sandra Incerpi, Sheng-Yang Lee, Hung-Yun Lin, Jaqueline Whang-Peng
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Heliyon, Vol 10, Iss 13, Pp e34006- (2024)
Druh dokumentu: article
ISSN: 2405-8440
DOI: 10.1016/j.heliyon.2024.e34006
Popis: Progesterone (P4) plays a pivotal role in regulating the cancer progression of various types, including breast cancer, primarily through its interaction with the P4 receptor (PR). In PR-negative breast cancer cells, P4 appears to function in mediating cancer progression, such as cell growth. However, the mechanisms underlying the roles of P4 in PR-negative breast cancer cells remain incompletely understood. This study aimed to investigate the effects of P4 on cell proliferation, gene expression, and signal transduction in PR-negative MDA-MB-231 breast cancer cells. P4-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 P4-induced extracellular signal-regulated kinase 1/2 (ERK1/2) activation, aligning with computational models of P4 binding to integrin αvβ3. Disrupting integrin αvβ3 binding with RGD peptide or anti-integrin αvβ3 antibody altered P4-induced expression of proliferative genes and modified P4-induced cell growth in breast cancer cells. In conclusion, integrin αvβ3 appears to mediate P4-induced ERK1/2 signal pathway to regulate proliferation via alteration of proliferation-related gene expression in PR-negative breast cancer cells.
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