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

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

  • Heliyon. 2024 Jul 2;10(13):e34006. doi: 10.1016/j.heliyon.2024.e34006.
Chung-Che Tsai 1 2,  Yung-Ning Yang 3 4,  Kuan Wang 2,  Yu-Chun E Chen 5,  Yi-Fong Chen 1,  Jen-Chang Yang 2,  Zi-Lin Li 1 2,  Haw-Ming Huang 6,  Jens Z Pedersen 7,  Sandra Incerpi 8,  Sheng-Yang Lee 6 9,  Hung-Yun Lin 1 10 11 12 13,  Jaqueline Whang-Peng 10
Affiliations

Affiliations

  • 1 Graduate Institute of Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan.
  • 2 Graduate Institute of Nanomedicine and Medical Engineering, College of Medical Engineering, Taipei Medical University, Taipei 11031, Taiwan.
  • 3 Department of Pediatrics, E-DA Hospital, I-Shou University, Kaohsiung 82445, Taiwan.
  • 4 School of Medicine, I-Shou University, Kaohsiung 82445, Taiwan.
  • 5 School of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan.
  • 6 School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei 11031, Taiwan.
  • 7 Department of Biology, University of Rome Tor Vergata, Rome 00133, Italy.
  • 8 Department of Sciences, University Roma Tre, Rome 00133, Italy.
  • 9 Dentistry, Wan-Fang Medical Center, Taipei Medical University, Taipei 11031, Taiwan.
  • 10 Cancer Center, Wan Fang Hospital, Taipei Medical University, Taipei 11031, Taiwan.
  • 11 Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Albany 12203, NY, USA.
  • 12 TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei 11031, Taiwan.
  • 13 Traditional Herbal Medicine Research Center of Taipei Medical University Hospital, Taipei Medical University, Taipei 11031, Taiwan.
PMID: 39071644 DOI: 10.1016/j.heliyon.2024.e34006
Abstract

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.

Keywords

Breast cancer; Integrin αvβ3; Progesterone; Progesterone receptor; Proliferation.

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