Progesterone modulates cell growth via integrin αvβ3-dependent pathway in progesterone receptor-negative MDA-MB-231 cells
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
Affiliations
Chung-Che Tsai
Graduate Institute of Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan; Graduate Institute of Nanomedicine and Medical Engineering, College of Medical Engineering, Taipei Medical University, Taipei 11031, Taiwan
Yung-Ning Yang
Department of Pediatrics, E-DA Hospital, I-Shou University, Kaohsiung 82445, Taiwan; School of Medicine, I-Shou University, Kaohsiung 82445, Taiwan
Kuan Wang
Graduate Institute of Nanomedicine and Medical Engineering, College of Medical Engineering, Taipei Medical University, Taipei 11031, Taiwan
Yu-Chun E. Chen
School of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan
Yi-Fong Chen
Graduate Institute of Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan
Jen-Chang Yang
Graduate Institute of Nanomedicine and Medical Engineering, College of Medical Engineering, Taipei Medical University, Taipei 11031, Taiwan
Zi-Lin Li
Graduate Institute of Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan; Graduate Institute of Nanomedicine and Medical Engineering, College of Medical Engineering, Taipei Medical University, Taipei 11031, Taiwan
Haw-Ming Huang
School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei 11031, Taiwan
Jens Z. Pedersen
Department of Biology, University of Rome Tor Vergata, Rome 00133, Italy
Sandra Incerpi
Department of Sciences, University Roma Tre, Rome 00133, Italy
Sheng-Yang Lee
School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei 11031, Taiwan; Dentistry, Wan-Fang Medical Center, Taipei Medical University, Taipei 11031, Taiwan; Corresponding author. No.250, Wuxing St., Xinyi Dist., Taipei 11031, Taiwan.
Hung-Yun Lin
Graduate Institute of Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan; Cancer Center, Wan Fang Hospital, Taipei Medical University, Taipei 11031, Taiwan; Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Albany 12203, NY, USA; TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei 11031, Taiwan; Traditional Herbal Medicine Research Center of Taipei Medical University Hospital, Taipei Medical University, Taipei 11031, Taiwan; Corresponding author. No.301, Yuantong Rd., Zhonghe Dist., New Taipei City 23564, Taiwan.
Jaqueline Whang-Peng
Cancer Center, Wan Fang Hospital, Taipei Medical University, Taipei 11031, Taiwan
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.
