GATA-3 is expressed in association with estrogen receptor in breast cancer.
To better understand the molecular basis for the hormone-responsive phenotype in breast cancer, we have used a human cDNA array to compare patterns of gene expression between breast carcinoma cell lines discordant for estrogen receptor (ER) expression. These experiments indicated abundant expression of the transcription factor GATA-3 in the ER-positive cell lines MCF7 and T-47D, with minimal or no expression in the ER-negative cells lines MDA-MB-231 and HBL-100. Northern blot analysis of a panel of human breast carcinoma cell lines demonstrated a correlation between ER and GATA-3 expression. Studies of MCF7 cells grown in the absence or presence beta-estradiol indicated that GATA-3 expression was not responsive to estradiol. Protein immunoprecipitation and gel shift analysis confirmed the presence of functional GATA-3 protein in MCF7 but not in HBL-100 nuclear extracts. A panel of 47 primary breast cancers was characterized for expression of ER and GATA-3 using immunoperoxidase assay. In primary tumors, a statistically significant correlation between ER and GATA-3 expression was established (p < 0.0001, chi2). Our results indicate that GATA-3, in association with ER, is likely to regulate genes critical to the hormone-responsive breast cancer phenotype.
Hoch
R V
RV
Department of Surgery, Stanford University, CA, USA.
Thompson
D A
DA
Baker
R J
RJ
Weigel
R J
RJ
D015152:Blotting, Northern; D001943:Breast Neoplasms / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D050990:GATA3 Transcription Factor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism; D015534:Trans-Activators / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D015534:Trans-Activators; D004958:Estradiol