Journal
ANTICANCER RESEARCH
Volume 38, Issue 8, Pages 4435-4441Publisher
INT INST ANTICANCER RESEARCH
DOI: 10.21873/anticanres.12745
Keywords
GATA3; breast cancer; transcription factor; mammary gland biology
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Funding
- Peter T. Rowley Breast Cancer Research Grant from the New York State Department of Health [C028250]
- Gundersen Medical Foundation
- NIH NIGMS IRACDA K12 [1K12GM102779-01]
- Albert Einstein Cancer Center [NIH P30 CA013330]
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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.
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