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

Heliyon (Jul 2024)

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

Journal volume & issue: Vol. 10, no. 13
p. e34006

Abstract

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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.

Published in Heliyon

ISSN: 2405-8440 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Science: Science (General); Social Sciences: Social sciences (General)
Website: https://www.cell.com/heliyon/home

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