Transcriptional up-regulation of PHLDA1 by 17β-estradiol in MCF-7 breast cancer cells

Autor(es)

A.C. Marchiori ^[1] ; D.A. Casolari ^[2] ; M.A. Nagai ^[3]

Afiliação do(s) autor(es)

^[1] Universidade de São Paulo. Faculdade de Medicina. Departamento de Radiologia - Brasil

^[2] Universidade de São Paulo. Faculdade de Medicina. Departamento de Radiologia - Brasil

^[3] Universidade de São Paulo. Faculdade de Medicina. Departamento de Radiologia - Brasil

• Tipo de documento: Artigo Científico
• Fonte: Brazilian Journal of Medical and Biological Research; v. 41, n. 7, p. 579-582, 2008-06-30.

Resumo

Most breast cancer risk factors are associated with prolonged exposure of the mammary gland to high levels of estrogens. The actions of estrogens are predominantly mediated by two receptors, ERα and ERβ, which act as transcription factors binding with high affinity to estrogen response elements in the promoter region of target genes. However, most target genes do not contain the consensus estrogen response elements, but rather degenerated palindromic sequences showing one or more mutations and other ER-binding sites such as AP-1 and SP-1. Using the differential display reverse transcription-polymerase chain reaction technique, our group identified several genes differentially expressed in normal tissue and in ER-positive and ER-negative primary breast tumors. One of the genes shown to be down-regulated in breast tumors compared to normal breast tissue was the PHLDA1 (Pleckstrin homology-like domain, family A, member 1). In the present study, we investigated the potential of PHLDA1 to be regulated by estrogen via ER in MCF-7 breast cancer cells. The promoter region of PHLDA1 shows an imperfect palindrome, an AP-1- and three SP-1-binding sites potentially regulated by estrogens. We also assessed the effects of 17β-estradiol on PHLDA1 mRNA expression in MCF-7 breast cancer cells. MCF-7 cells exposed to 10 nM 17β-estradiol showed more than 2-fold increased expression of the PHLDA1 transcripts compared to control cells (P = 0.05). The anti-estrogen ICI 182,780 (1 µM) inhibited PHLDA1 mRNA expression and completely abolished the effect of 10 nM 17β-estradiol on PHLDA1 expression (P < 0.05), suggesting that PHLDA1 is regulated by estrogen via ER. (AU)

• Processo FAPESP: 04/04607-8 - Sinalização heterotípica entre células epiteliais tumorais e fibroblastos no carcinoma de mama
• Beneficiário: Maria Mitzi Brentani
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• 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