GATA3 protein as a MUC1 transcriptional regulator in breast cancer cellsReportar como inadecuado




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Breast Cancer Research

, 8:R64

First Online: 01 November 2006Received: 01 May 2006Revised: 22 July 2006Accepted: 01 November 2006

Abstract

IntroductionRecent studies have demonstrated that members of the GATA-binding protein GATA family GATA4 and GATA5 might have pivotal roles in the transcriptional upregulation of mucin genes MUC2, MUC3 and MUC4 in gastrointestinal epithelium. The zinc-finger GATA3 transcription factor has been reported to be involved in the growth control and differentiation of breast epithelial cells. In SAGE serial analysis of gene expression studies we observed an intriguing significant correlation between GATA3 and MUC1 mRNA expression in breast carcinomas. We therefore designed the present study to elucidate whether MUC1 expression is regulated by GATA3 in breast cancer cells.

MethodsPromoter sequence analysis of the MUC1 gene identified six GATA cis consensus elements in the 5- flanking region GATA1, GATA3 and four GATA-like sequences. Chromatin immunoprecipitation and electrophoretic mobility-shift assays were employed to study the presence of a functional GATA3-binding site. GATA3 and MUC1 expression was analyzed in vitro with a GATA3 knockdown assay. Furthermore, expression of GATA3 and MUC1 genes was analyzed by real-time RT-PCR and immunohistochemistry on breast cancer-specific tissue microarrays.

ResultsWe confirmed the presence of a functional GATA3-binding site on the MUC1 promoter region in the MCF7 cell line. We determined that GATA3 knockdown assays led to a decrease in MUC1 protein expression in MCF7 and T47D cells. In addition, we detected a statistically significant correlation in expression between GATA3 and MUC1 genes at the mRNA and protein levels both in normal breast epithelium and in breast carcinomas p = 0.01. GATA3 expression was also highly associated with estrogen receptor and progesterone receptor status p = 0.0001 and tumor grade p = 0.004 in breast carcinomas.

ConclusionOur study provides evidence indicating that GATA3 is probably a mediator for the transcriptional upregulation of MUC1 expression in some breast cancers.

Abbreviationsbpbase pairs

ChIPchromatin immunoprecipitation

DABdiaminobenzidine

DTTdithiothreitol

ELISAenzyme-linked immunosorbent assay

EMSAelectrophoretic mobility-shift assay

ERestrogen receptor

ESR1gene encoding estrogen receptor α

GATA3GATA-binding protein 3

HRPhorseradish peroxidase

IDCinvasive ductal carcinoma

MUC1mucin 1

PRprogesterone receptor

RT-PCRreverse-transcriptase-mediated polymerase chain reaction

SAGEserial analysis of gene expression

TMAtissue microarray.

Electronic supplementary materialThe online version of this article doi:10.1186-bcr1617 contains supplementary material, which is available to authorized users.

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Autor: Martín C Abba - María I Nunez - Andrea G Colussi - María V Croce - Amada Segal-Eiras - C Marcelo Aldaz

Fuente: https://link.springer.com/







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