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
  • 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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