Down-regulation of MHC class I antigen in insulinoma cells controlled by the R1 element of the H-2 enhancer

Xuehai Ye, Anastasia Kralli, Ruowen Ge, Robert P. Ricciardi, Barbara B. Knowles

Research output: Contribution to journalArticle

Abstract

Tumorigenesis in mice of the rat insulin promoter [RIP]simian virus 40 tumor antigen [SV40 Tag] transgenic lineages, RIP1-Tag2 and RIP1-Tag4, is a process initiated by expression of SV40 Tag in pancreatic β cells, evolution of islet cell hyperplasia and insulinoma appearance. Analysis of major histocompatibility complex [MHC] class I gene expression during this process revealed a normal level of MHC class I molecules at the surface of pancreatic islet cells of RIP1-Tag4 mice, while hyperplastic islets from the same mice contained cells expressing a normal level and cells expressing a low level of MHC class I antigen. Insulinomas themselves expressed very low levels or no MHC class I gene product. Thus, down-regulation of MHC class I gene appears to accompany tumor progression of SV40 Tag-transformed ,B islet cells. MHC class I antigen expression in a series of clonally derived cell lines of β cell origin from different SV40 Tag-induced insulinomas ranged from quite low to undetectable, although expression was inducible by interferon-γ. Nuclear run-on and transient transfection analyses indicated that expression of the MHC class I gene in these cells is controlled at the transcriptional level, and that the decreased expression is paralleled by reduced binding of transcription factors to the R1 element of the H-2 enhancer.

Original languageEnglish (US)
Pages (from-to)1195-1204
Number of pages10
JournalOncogene
Volume9
Issue number4
StatePublished - Apr 1 1994
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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