Mutant GATA3 Actively Promotes the Growth of Normal and Malignant Mammary Cells.
Mutant GATA3 Actively Promotes the Growth of Normal and Malignant Mammary Cells.
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DOI：
10.21873/anticanres.12745
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发表时间：
2018-08
影响因子：
2
通讯作者：
Kenny PA
中科院分区：
文献类型：
--
作者：
Emmanuel N;Lofgren KA;Peterson EA;Meier DR;Jung EH;Kenny PA
GATA3是一种在乳腺腔上皮细胞中表达的转录因子，是乳腺发育所必需的。GATA3杂合突变出现在高达15%的雌激素受体(ER)阳性的乳腺肿瘤中，并被认为是零等位基因，导致单倍性功能不足；然而，乳腺癌的GATA3突变谱与HDR综合征(一种真正的GATA3单倍性功能不全疾病)的突变谱形成鲜明对比。材料和转基因小鼠、3D培养和异种移植，检测突变型GATA3表达对乳腺细胞增殖的影响。突变的GATA3促进了ZR751细胞异种移植瘤的生长，并促进了转基因小鼠乳腺小叶肺泡性早熟的发育。这些数据表明，最近在乳腺癌中发现的GATA3突变编码了活跃的转录因子，这些转录因子诱导了正常乳腺上皮的增殖表型，并促进了ER阳性乳腺癌细胞的生长。
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 Transgenic mice, 3D cultures and xenografts were used to examine the effect of mutant GATA3 expression on mammary cell proliferation. Mutant GATA3 accelerated tumor growth of ZR751 cell xenografts and promoted precocious lobuloalveolar development in transgenic mouse mammary glands. These data indicate that the 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.