GATA-3 transcription factor as a putative MUC-1 gene expression regulator in breast cancer cells

ABBA MC; NUNEZ MI; ALDAZ CM; CROCE MV; SEGAL-EIRAS A

Córdoba, Argentina

Congreso; VII Latin American Congress of Immunology (ALAI); 2005

Sociedad Latinoamericana de Histocompatibilidad (SLAH)

The aim of the current study was to elucidate whether or not expression of MUC-1 gene is regulated by GATA-3 in breast carcinogenesis. Serial Analysis of Gene Expression (SAGE) profiling in 47 breast libraries: 4 normal tissue, 8 ductal carcinoma in situ (DCIS), 33 invasive ductal carcinoma (IDC) and 2 cell lines showed an unique pattern of GATA-3 expression compared with others GATA family members. Promoter sequences analysis identified six GATA-cis elements in the 5´ flanking region of MUC-1 gene (GATA-1, GATA-3 and four GATA-like sequences). Chromatin-immunoprecipitation assay confirmed the presence of a functional GATA-3 binding site on the MUC-1 promoter region in MCF-7 cell line. Furthermore, expression of GATA-3 and MUC-1 genes was studied by real time RT-PCR (n=37) and tissue-microarray immunohistochemistry (n=225) in a panel of normal, DCIS and IDC. These data showed a correlation between the expression of both genes at mRNA and protein levels in normal breast epithelium (r=0.78, p=0.001) and breast carcinomas (r=0.60, p<0.0001). Moreover, GATA-3 expression was highly associated with low tumor grade (p=0.004). Our study provides evidences for GATA-3 mediated transcriptional up-regulation of MUC-1 expression in breast cancer cells.