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SV40-IMMORTALIZED NON-TUMORIGENIC AND TUMORIGENIC CELL LINES DIFFER IN EXPRESSION OF HALLMARK VIRAL RESPONSE MRNAS
Citation:
Crosby, L. M., G. R. Benavides, H. Ni, L. Yoon, K. T. Morgan, AND A B. DeAngelo. SV40-IMMORTALIZED NON-TUMORIGENIC AND TUMORIGENIC CELL LINES DIFFER IN EXPRESSION OF HALLMARK VIRAL RESPONSE MRNAS. Presented at 2001 Annual Meeting of the American Association for Cancer Research, New Orleans, LA, 3/24-28/2001.
Description:
SV40-Immortalized Non-Tumorigenic and Tumorigenic Cell Lines Differ in Expression of Hallmark Viral Response mRNAs.
Prior to the use of an in vitra/in viva transformation system to examine the tumorigenic activity of environmental contaminants, in vitra gene expression patterns were compared on 1200-gene arrays using the SV40 immortalized, non-tumorigenic cell line, SV-HUC-1, and the 3-methylcholanthrene transformed tumorigenic line, MC-SV-HUC-T-2 (ATCC). Selected differences were confirmed by real-time PCR. Differences between the tumorigenic vs non-tumorigenic cell line were concordant with known responses to SV 40 transfection. Gene expression was consistent with binding and inactivation of pRB, allowing removal of the restriction point blockage of the cell cycle. We observed p16INK4 upregulation, as reported by others. Since p16INK4 requires active pRB in order to block cell cycle progression, its upregulation would not be expected to successfully block the cell cycle, and indeed, upregulation of cyclin D2, DP1, DP2 and CDK2/4 indicated that progression to S-phase is unimpeded. The most highly upregulated mRNA was the oncogene/putative inflammatory mediator, neutrophil gelatinase- associated lipocalin precursor (NGAL, 29.2-fold). Many changes related to antiviral activity were present: IFI56, 9-27, MxA and MxAB and 2',5'-oligoadenylate synthetases 1 and 2 were upregulated (cellular interferon-responsive gene products previously shown to become activated in response to hel-pes simplex type 1, Thogoto and human influenza C viruses). Other interferon upregulation responses included p68 kinase, interferon- inducible protein 1-8D + 1-8U, leukocyte interferon-inducible peptide, interferon a- induced 11.5 kDa protein and IFN-a/B receptor subunit precursor; IFNy receptor downregulation occurred. All -150 changes were significant at p<0.05 (n=5). These changes indicate a continuum of graded SV40-related gene expression between these two SV 40-immortalized cell lines and viral response activation due strictly to prior in vitra 3- methylcholanthrene transformation, since observed gene expression responses were largely attributable to the presence of viral element(s). The complex transcriptional differences between these cells should be considered when using this biologic system for in vitra/in viva tumorigenesis assays.
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