Insulin-like growth factor-1 and 17β-estradiol down-regulate prostate apoptosis response-4 expression in MCF-7 breast cancer cells

  • Authors:
    • Debora A. Casolari
    • Michelly C. Pereira
    • Simone A. de Bessa Garcia
    • Maria A. Nagai
  • View Affiliations

  • Published online on: May 6, 2011     https://doi.org/10.3892/ijmm.2011.691
  • Pages: 337-342
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Abstract

The PKC apoptosis WT1 regulator gene, also named prostate apoptosis response-4 (PAR-4), encodes a pro-apoptotic protein that sensitizes cells to numerous apoptotic stimuli. Insulin-like growth factor-1 (IGF-1) and 17β-estradiol (E2), two important factors for breast cancer development and progression, have been shown to down-regulate PAR-4 expression and inhibit apoptosis induced by PAR-4 in neuronal cells. In this study, we sought to investigate the mechanisms of regulation of PAR-4 gene expression in MCF-7 cells treated with E2 or IGF-1. E2 (10 nM) and IGF-1 (12.5 nM) each down-regulated PAR-4 expression in MCF-7 cells after 24 h of treatment. The effect of E2 was dependent on ER activation, as demonstrated by an increase in PAR-4 expression when cells were pretreated for 1 h with 1 µM ICI-182,780 (ICI) before receiving E2 plus ICI. The effect of IGF-1 was abolished by pre-treatment for 1 h with 30 µM LY294002 (a specific PI3-K inhibitor), and significantly inhibited by 30 µM SB202190 (a specific p38MAPK inhibitor). We also demonstrated that E2 acts synergistically with IGF-1, resulting in greater down-regulation of PAR-4 mRNA expression compared with E2 or IGF-1 alone. Our results show for the first time that E2 and IGF-1 inhibit PAR-4 gene expression in MCF-7 cells, suggesting that this down-regulation may provide a selective advantage for breast cancer cell survival.

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September 2011
Volume 28 Issue 3

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Casolari DA, Pereira MC, de Bessa Garcia SA and Nagai MA: Insulin-like growth factor-1 and 17β-estradiol down-regulate prostate apoptosis response-4 expression in MCF-7 breast cancer cells. Int J Mol Med 28: 337-342, 2011
APA
Casolari, D.A., Pereira, M.C., de Bessa Garcia, S.A., & Nagai, M.A. (2011). Insulin-like growth factor-1 and 17β-estradiol down-regulate prostate apoptosis response-4 expression in MCF-7 breast cancer cells. International Journal of Molecular Medicine, 28, 337-342. https://doi.org/10.3892/ijmm.2011.691
MLA
Casolari, D. A., Pereira, M. C., de Bessa Garcia, S. A., Nagai, M. A."Insulin-like growth factor-1 and 17β-estradiol down-regulate prostate apoptosis response-4 expression in MCF-7 breast cancer cells". International Journal of Molecular Medicine 28.3 (2011): 337-342.
Chicago
Casolari, D. A., Pereira, M. C., de Bessa Garcia, S. A., Nagai, M. A."Insulin-like growth factor-1 and 17β-estradiol down-regulate prostate apoptosis response-4 expression in MCF-7 breast cancer cells". International Journal of Molecular Medicine 28, no. 3 (2011): 337-342. https://doi.org/10.3892/ijmm.2011.691