Characterization of a gastric tumor cell line defective in MHC class I inducibility by both α‐ and γ‐interferon

Abstract

Alpha/beta and gamma type interferons (IFN), act through distinct cell surface receptors and induce transcription of an overlapping sets of genes. MHC class I genes are inducible by both type of interferons. We have analyzed a gastric tumor cell line, AGS, which was completely defective in MHC class I response to interferon-alpha and gamma. Northern blot analysis demonstrated that the lack of IFN response was related with the absence of up-regulation of specific HLA class I mRNA. Electrophoretic mobility shift assays in various tumor cell lines after IFN-alpha and IFN-gamma treatment showed differential binding of the transcriptional factors to MHC class I regulatory elements. Comparison of kappa-B binding activity showed that IFN-alpha and IFN-gamma induced opposite changes in NF-kappa B binding activity in AGS cells, indicating that the absence of MHC class I response in AGS appears to be independent of kappa-B activity. In contrast, there were remarkable differences in the level of transcriptional factor binding to an interferon-responsive sequence element (IRSE), between AGS and other interferon-responsive tumor cell lines. This result suggests that the low level of transcriptional factor binding to IRSE in AGS cells was responsible of the lack of induction of MHC class I antigens. In this context, overlapping factors in the signal transduction pathway of both type I and II interferons may be involved in the non-responsiveness of this gastric carcinoma tumor cell line.

Differentially Regulated Interferon Response Determines the Outcome of Newcastle Disease Virus Infection in Normal and Tumor Cell Lines

“…Defects in IFN response occur in tumor cells (1,11,38,44,50,(53)(54)(55). These lesions usually reside in the components of the IFN response pathway such as STAT1.…”

“…Many types of tumor cells harbor defects in IFN response (1,11,38,44,50,54,55), and some viruses, such as the vesicular stomatitis virus, exploit this defect to cause virusmediated oncolysis (2,37,51).…”

Direct growth suppressive activity of interferon-? and -? on human gastric cancer cells

“…M, 100 base pair DNA marker; T, DNA sample prepared from ␥-irradiated thymus gland; C, control media; ␥, IFN-␥ treated media. AGS cells is supported by low levels of transcriptional factor binding to an interferon-responsive sequence element [27]. IFN-␣ suppressed cell growth through induction of cell cycle arrest only, whereas both apoptotic cell death and cell cycle arrest were responsible for IFN-␥-mediated growth suppression.…”

Oncolytic Viruses for Cancer Therapy II. Cell-Internal Factors for Conditional Growth in Neoplastic Cells

“…Resistance to the actions of IFN can occur at many levels, due to the manifold and complex responses elicited by IFNs. Accordingly, a great number of abnormalities associated with defective IFN responses have been reported in cancer cells [46][47][48]. If defects in cancer cells render them unresponsive to IFNs, they would also be expected to become vulnerable to virus infection.…”