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Breast Cancer Research and Treatment
Published in: Breast Cancer Research and Treatment 3/2008

01-06-2008 | Preclinical Study

Precancerous model of human breast epithelial cells induced by NNK for prevention

Authors: Nalin Siriwardhana, Shambhunath Choudhary, Hwa-Chain Robert Wang

Published in: Breast Cancer Research and Treatment | Issue 3/2008

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Abstract

Epidemiological investigations have suggested that exposure to tobacco and environmental carcinogens increase the risk of developing human breast cancer. In light of the chronic exposure of human breast tissues to tobacco and environmental carcinogens, we have taken an approach of analyzing cellular changes of immortalized non-cancerous human breast epithelial MCF10A cells during the acquisition of cancerous properties induced by repeated exposure to the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) at a low concentration of 100 pM. We found that accumulated exposures of MCF10A cells to NNK result in progressive development of cellular carcinogenesis from a stage of immortalization to precancerous sub-stages of acquiring a reduced dependence on growth factors and acquiring anchorage-independent growth. Using Matrigel for MCF10A cells to form size-restricted acini, we detected that exposures to NNK resulted in altered acinar conformation. Analysis of gene expression profiles by cDNA microarrays revealed up- and down-regulated genes associated with NNK-induced carcinogenesis. Using this cellular carcinogenesis model as a target system to identify anticancer agents, we detected that grape seed proanthocyanadin extract significantly suppressed NNK-induced carcinogenesis of MCF10A cells. Our studies provide a carcinogenesis-cellular model mimicking the accumulative exposure to carcinogens in the progression of human breast epithelial cells to increasingly acquire cancerous properties, as likely occurs in the development of precancerous human breast cells. Our cellular model also serves as a cost-efficient, in vitro system to identify preventive agents that inhibit human breast cell carcinogenesis induced by chronic exposures to carcinogens.
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Metadata
Title
Precancerous model of human breast epithelial cells induced by NNK for prevention
Authors
Nalin Siriwardhana
Shambhunath Choudhary
Hwa-Chain Robert Wang
Publication date
01-06-2008
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 3/2008
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-007-9666-9

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