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

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

Full text
Author(s):
A.C. Marchiori [1] ; D.A. Casolari [2] ; M.A. Nagai [3]
Total Authors: 3
Affiliation:
[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
Total Affiliations: 3
Document type: Journal article
Source: Brazilian Journal of Medical and Biological Research; v. 41, n. 7, p. 579-582, 2008-06-30.
Abstract

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)

FAPESP's process: 04/04607-8 - Heterotypic signaling between epithelial tumor cells and fibroblasts in carcinoma of the breast
Grantee:Maria Mitzi Brentani
Support Opportunities: Research Projects - Thematic Grants
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