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Cigarette smoke condensate-induced transformation of normal human breast epithelial cells in vitro

Oncogene volume 23, pages 5880–5889 (2004)Cite this article

Abstract

In the present study, we showed that a single-dose treatment of normal breast epithelial cell line, MCF10A, for 72 h with cigarette smoke condensate (CSC) resulted in a transformed phenotype. The anchorage-dependent growth of these cells was decreased due to increased cell cycle arrest in S–G2/M phase; however, the surviving cells developed resistance due to an increased Bcl-xL to Bax ratio. Levels of PCNA and gadd45 proteins – involved in DNA repair in response to genomic damage – were increased, suggesting that the cells were responding to CSC-induced genomic damage. The transformation of MCF10A cells was determined by their colony-forming efficiency in soft-agar in an anchorage-independent manner. CSC-treated MCF10A cells efficiently formed colonies in soft-agar. We then re-established cell lines from the soft-agar colonies and further examined the persistence of their transforming characteristics. The re-established cell lines, when plated after 17 passages without CSC treatment, still formed colonies in the soft-agar. An increased staining of neuropilin-1 (NRP-1) further showed a transformation characteristic of MCF10A cells treated with CSC. In summary, our results suggest that CSC is capable of transforming the MCF10A cells in vitro, supporting the role of cigarette smoking and increased risk for breast cancer.

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Acknowledgements

We are grateful to Dr Fazlul Sarkar from the Wayne State University School of Medicine, Detroit, MI, for providing the MCF10A cell line and to Dr Sushant K Banerjee from the Cancer Research Unit, VA Medical Center, Research Division, Kansas City, MO, for his advice on the NRP-1 immunohistochemistry as well as Santhi Konduri for her help in the quantification of the RPA results. We are also thankful to Mary Wall for proofreading the manuscript. This work was supported by the Flight Attendants Medical Research Institute, Miami, FL to Satya Narayan.

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Authors and Affiliations

  1. Department of Anatomy and Cell Biology, UF Shands Cancer Center, Academic Research Building, Room R4-216, PO Box 100232, University of Florida, Gainesville, 32610, FL, USA

    Satya Narayan, Aruna S Jaiswal & Diana Kang

  2. Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, 14263, New York, USA

    Pratima Srivastava & Gokul M Das

  3. Division of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, 40536, KY, USA

    C Gary Gairola

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  1. Satya Narayan
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Correspondence to Satya Narayan.

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Narayan, S., Jaiswal, A., Kang, D. et al. Cigarette smoke condensate-induced transformation of normal human breast epithelial cells in vitro. Oncogene 23, 5880–5889 (2004). https://doi.org/10.1038/sj.onc.1207792

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