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  • Original Paper
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Human mammary epithelial cells exhibit a differential p53-mediated response following exposure to ionizing radiation or UV light

Oncogene volume 18, pages 5795–5805 (1999)Cite this article

Abstract

The tumor suppressor protein, p53, plays a critical role as a transcriptional activator of downstream target genes involved in the cellular response to DNA damaging agents. We examined the cell cycle checkpoint response of human mammary epithelial cells (HMEC) and their isogenic fibroblast counterparts to ionizing (IR) and ultraviolet (UV) radiation, two genotoxic agents whose DNA damage response pathways involve p53. Using flow cytometric analysis, we found that both mortal and immortalized HMEC, which contain wild-type p53 sequence, do not exhibit a G1 arrest in response to IR, but show an intact G2 checkpoint. Supportive evidence from Western analyses revealed that there was neither an increase in p53 nor one of its downstream targets, p21WAF1, in HMEC exposed to IR. In contrast, isogenic mammary fibroblasts arrest at the G1 checkpoint and induce the p53 and p21WAF1 proteins following IR. By comparison, HMEC exposed to UV displayed an S phase arrest and induced the expression of p53 and p21WAF1. Our results show that the cellular response to DNA damage depends on both the type of damage introduced into the DNA and the specific cell type.

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Acknowledgements

We are grateful to Dr William K Kaufmann for enlightening discussions and critical reading of the manuscript. This research was supported by US Public Health Service Grants CA62059 and CA40453 from the National Cancer Institute, and a predoctoral (KMM) and postdoctoral (SMH) traineeship (T32 ES07126) from the National Institute of Environmental Health Sciences.

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Authors and Affiliations

  1. Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, 27599, North Carolina, NC, USA

    Karen M Meyer, Suzanne M Hess & Steven A Leadon

  2. Curriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, 27599, North Carolina, NC, USA

    Karen M Meyer & Steven A Leadon

  3. Department of Pathology, University of California at San Francisco, San Francisco, 94143, California, CA, USA

    Thea D Tlsty

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  1. Karen M Meyer
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Meyer, K., Hess, S., Tlsty, T. et al. Human mammary epithelial cells exhibit a differential p53-mediated response following exposure to ionizing radiation or UV light. Oncogene 18, 5795–5805 (1999). https://doi.org/10.1038/sj.onc.1202977

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