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

Autor(es)

Casolari, Debora A. ^[1] ; Pereira, Michelly C. ^[1] ; De Bessa Garcia, Simone A. ^[1] ; Nagai, Maria A. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Disciplina Oncol, Dept Radiol, Fac Med, BR-01246903 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: International Journal of Molecular Medicine; v. 28, n. 3, p. 337-342, SEP 2011.
• Citações Web of Science: 7

Resumo

The PKC apoptosis WTI 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 17 beta-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 mu M ICI-182,780 (ICI) before receiving E2 plus ICI. The effect of IGF-1 was abolished by pre-treatment for 1 h with 30 mu M LY294002 (a specific PI3-K inhibitor), and significantly inhibited by 30 mu M 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. (AU)

• Processo FAPESP: 06/01026-0 - Análise funcional de genes potencialmente regulados pelo receptor de estrógeno e/ou pelo oncogene ERBB2: implicações no diagnóstico, prognóstico e tratamento do câncer de mama
• Beneficiário: Maria Aparecida Nagai
• Modalidade de apoio: Auxílio à Pesquisa - Temático