Breast Cancer Research and Treatment

, Volume 79, Issue 1, pp 95–105 | Cite as

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


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 cancer human breast epithelial cells MCF10A NNK tobacco-specific carcinogen tumor 


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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

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