Transformation of Non-Cancerous Human Breast Epithelial Cell Line MCF10A by the Tobacco-Specific Carcinogen NNK

被引：0
作者：
Jianxun Mei
Hongbo Hu
Michael McEntee
Howard Plummer III
Ping Song
Hwa-Chain R. Wang
机构：
[1] The University of Tennessee,Department of Comparative Medicine
[2] The University of Tennessee,Department of Pathology, College of Veterinary Medicine
来源：
Breast Cancer Research and Treatment | 2003年 / 79卷
关键词：
human breast cancer; human breast epithelial cells; MCF10A; NNK; tobacco-specific carcinogen; tumor;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
Repeated treatments of non-cancerous human breast epithelial cells MCF10A with a low dose of the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induced the development of cancerous cells. NNK-transformed MCF10A cells acquired cancerous properties including anchorage-independent cell growth and increased cell motility. Cellular transformation of MCF10A cells was accompanied by a loss of responsiveness to 17β-estradiol and decreased rate of cell proliferation. NNK-transformed MCF10A cells were also tumorigenic in immunodifficient mice. Studies of changes in the regulation of intracellular signaling pathways revealed that the upstream Erk pathway was down-regulated in the NNK-transformed cells. Our data provide the first evidence suggesting that the tobacco carcinogen NNK is competent to induce malignant transformation of non-cancerous human breast epithelial cells. Our findings suggest that the tobacco carcinogen NNK may contribute to early events in human breast carcinogenesis.
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页码：95 / 105
页数：10
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