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Insulin-like growth factor binding protein-3 induces senescence by inhibiting telomerase activity in MCF-7 breast

Ahreum Kwon1, Hyun Wook Chae1, Woo Jung Lee1

  • 1Department of Pediatrics, Severance Children's Hospital, Endocrine Research Institute, College of Medicine, Yonsei University, Seoul, 03722, South Korea.

Scientific Reports
|May 30, 2023
PubMed

Insights

Insulin-like growth factor binding protein-3 (IGFBP-3) induces breast cancer cell senescence by suppressing telomerase activity. This finding reveals IGFBP-3 as a potential therapeutic target for inhibiting MCF-7 breast cancer cell proliferation.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Insulin-like growth factor binding protein-3 (IGFBP-3) is recognized for its potential tumor-suppressing capabilities.
  • IGFBP-3's role in cell proliferation inhibition varies based on cell type.

Purpose of the Study:

  • To investigate if IGFBP-3 induces cellular senescence in MCF-7 breast cancer cells.
  • To determine if IGFBP-3 suppresses telomerase activity, thereby inhibiting cancer cell proliferation.

Main Methods:

  • MCF-7 cells were induced to express IGFBP-3.
  • Flow cytometry assessed cell cycling and viability.
  • Senescence was evaluated using senescence-associated β-galactosidase activity.
  • Telomerase activity was measured via telomeric repeat amplification and real-time PCR for hTR and hTERT components.

Main Results:

  • IGFBP-3 induction led to decreased MCF-7 cell viability and a higher percentage of non-cycling cells.
  • Morphological changes indicative of a senescence-like phenotype were observed.
  • Senescence-associated β-galactosidase activity was significantly higher in IGFBP-3 expressing cells.
  • IGFBP-3 dose-dependently reduced telomerase activity by decreasing hTR and hTERT levels.

Conclusions:

  • IGFBP-3 induces cellular senescence in MCF-7 breast cancer cells.
  • IGFBP-3 inhibits cancer cell proliferation by suppressing telomerase activity.
  • IGFBP-3 acts as a negative regulator of MCF-7 breast cancer cell growth.

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