Transformation of non-cancerous human breast epithelial cell line MCF10A by the tobacco-specific carcinogen NNK.
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 17beta-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.
Mei
Jianxun
J
Department of Comparative Medicine, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN 37996, USA.
Hu
Hongbo
H
McEntee
Michael
M
Plummer
Howard
H
Song
Ping
P
Wang
Hwa-Chain R
HC
D000818:Animals; D001940:Breast / Q000166:cytology*; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000633:toxicity*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009602:Nitrosamines / Q000633:toxicity*; D036401:Toxicity Tests, Chronic
D002273:Carcinogens; D009602:Nitrosamines; D004958:Estradiol; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone