Breast Cancer Research and Treatment

, Volume 79, Issue 1, pp 95–105

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

  • Jianxun Mei
  • Hongbo Hu
  • Michael McEntee
  • Howard Plummer III
  • Ping Song
  • Hwa-Chain R. Wang
Article

DOI: 10.1023/A:1023326121951

Cite this article as:
Mei, J., Hu, H., McEntee, M. et al. Breast Cancer Res Treat (2003) 79: 95. doi:10.1023/A:1023326121951

Abstract

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.

human breast cancerhuman breast epithelial cellsMCF10ANNKtobacco-specific carcinogentumor

Copyright information

© Kluwer Academic Publishers 2003

Authors and Affiliations

  • Jianxun Mei
    • 1
  • Hongbo Hu
    • 1
  • Michael McEntee
    • 2
  • Howard Plummer III
    • 2
  • Ping Song
    • 1
  • Hwa-Chain R. Wang
    • 1
  1. 1.Department of Comparative MedicineThe University of TennesseeKnoxvilleUSA
  2. 2.Department of Pathology, College of Veterinary MedicineThe University of TennesseeKnoxvilleUSA