Mutant GATA3 Actively Promotes the Growth of Normal and Malignant Mammary Cells.

ABSTRACT

BACKGROUND/AIM: GATA3, a transcription factor expressed in luminal breast epithelial cells, is required for mammary gland development. Heterozygous GATA3 mutations occur in up to 15% of estrogen receptor (ER)-positive breast tumors and have been proposed to be null alleles resulting in haploinsufficiency; however, the mutation spectrum of GATA3 in breast cancer is in sharp contrast to that found in HDR syndrome, a true GATA3 haploinsufficiency disease. MATERIALS AND METHODS: Transgenic mice, 3D cultures and xenografts were used to examine the effect of mutant GATA3 expression on mammary cell proliferation. RESULTS: Mutant GATA3 accelerated tumor growth of ZR751 cell xenografts and promoted precocious lobuloalveolar development in transgenic mouse mammary glands. CONCLUSION: GATA3 mutations, recently observed in breast cancer, encode active transcription factors, which elicit proliferative phenotypes in normal mammary epithelium and promote the growth of ER-positive breast cancer cell lines.