Transformation of SV40-immortalized human uroepithelial cells by 3-methylcholanthrene increases IFN- and Large T Antigen-induced transcripts Public Deposited

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Creator
  • Yoon, Lawrence W
    • Other Affiliation: Glaxo SmithKline, Inc., Research Triangle Park, USA
  • DeAngelo, Anthony B
    • Other Affiliation: Environmental Carcinogenesis Division, National Health Effects and Environmental Research Laboratory, US Environmental Protection Agency, Research Triangle Park, USA
  • Ni, Hong
    • Other Affiliation: Glaxo SmithKline, Inc., Research Triangle Park, USA
  • Easton, Marilyn J
    • Other Affiliation: Glaxo SmithKline, Inc., Research Triangle Park, USA
  • Morgan, Kevin T
    • Other Affiliation: Sanofi-Aventis Pharmaceuticals, Inc., Bridgewater, USA
  • Moore, Tanya M
    • Other Affiliation: Environmental Carcinogenesis Division, National Health Effects and Environmental Research Laboratory, US Environmental Protection Agency, Research Triangle Park, USA
  • Crosby, Lynn M
    • Affiliation: School of Medicine, Curriculum in Toxicology
    • Other Affiliation: Environmental Carcinogenesis Division, National Health Effects and Environmental Research Laboratory, US Environmental Protection Agency, Research Triangle Park, USADepartment of Physiology, University of Tennessee Health Science Center, Memphis, USA
  • George, Michael
    • Other Affiliation: Environmental Carcinogenesis Division, National Health Effects and Environmental Research Laboratory, US Environmental Protection Agency, Research Triangle Park, USA
Abstract
  • Abstract Background Simian Virus 40 (SV40) immortalization followed by treatment of cells with 3-methylcholanthrene (3-MC) has been used to elicit tumors in athymic mice. 3-MC carcinogenesis has been thoroughly studied, however gene-level interactions between 3-MC and SV40 that could have produced the observed tumors have not been explored. The commercially-available human uroepithelial cell lines were either SV40-immortalized (HUC) or SV40-immortalized and then 3-MC-transformed (HUC-TC). Results To characterize the SV40 - 3MC interaction, we compared human gene expression in these cell lines using a human cancer array and confirmed selected changes by RT-PCR. Many viral Large T Antigen (Tag) expression-related changes occurred in HUC-TC, and it is concluded that SV40 and 3-MC may act synergistically to transform cells. Changes noted in IFP 9-27, 2'-5' OAS, IF 56, MxA and MxAB were typical of those that occur in response to viral exposure and are part of the innate immune response. Because interferon is crucial to innate immune host defenses and many gene changes were interferon-related, we explored cellular growth responses to exogenous IFN-γ and found that treatment impeded growth in tumor, but not immortalized HUC on days 4 - 7. Cellular metabolism however, was inhibited in both cell types. We conclude that IFN-γ metabolic responses were functional in both cell lines, but IFN-γ anti-proliferative responses functioned only in tumor cells. Conclusions Synergism of SV40 with 3-MC or other environmental carcinogens may be of concern as SV40 is now endemic in 2-5.9% of the U.S. population. In addition, SV40-immortalization is a generally-accepted method used in many research materials, but the possibility of off-target effects in studies carried out using these cells has not been considered. We hope that our work will stimulate further study of this important phenomenon.
Date of publication
Identifier
  • 20178601
  • doi:10.1186/1475-2867-10-4
Resource type
  • Article
Rights statement
  • In Copyright
Rights holder
  • Lynn M Crosby et al.; licensee BioMed Central Ltd.
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Journal title
  • Cancer Cell International
Journal volume
  • 10
Journal issue
  • 1
Page start
  • 4
Language
  • English
Is the article or chapter peer-reviewed?
  • Yes
ISSN
  • 1475-2867
Bibliographic citation
  • Cancer Cell International. 2010 Feb 23;10(1):4
Access
  • Open Access
Publisher
  • BioMed Central Ltd
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