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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
Casolari, Debora A. [1] ; Pereira, Michelly C. [1] ; De Bessa Garcia, Simone A. [1] ; Nagai, Maria A. [1]
Total Authors: 4
Affiliation:
[1] Univ Sao Paulo, Disciplina Oncol, Dept Radiol, Fac Med, BR-01246903 Sao Paulo - Brazil
Total Affiliations: 1
Document type: Journal article
Source: International Journal of Molecular Medicine; v. 28, n. 3, p. 337-342, SEP 2011.
Web of Science Citations: 7
Abstract

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)

FAPESP's process: 06/01026-0 - Functional characterization of genes potentially regulated by estrogen receptor and/or ERBB2 oncogene: implications in the diagnosis, prognosis and treatment of breast cancer
Grantee:Maria Aparecida Nagai
Support Opportunities: Research Projects - Thematic Grants