Induction of intercellular adhesion molecule 1 and class II histocompatibility antigens in colorectal tumour cells expressing activated ras oncogene

Abstract

Aims-To determine whether there is a correlation between activation of the ras oncogene and the induction of MHC class II antigens and intercellular adhesion molecule 1 (ICAM-1) by interferon-gamma (IFN-gamma).Methods-Expression of class II antigens, ICAM-1 and intracellular ras oncoprotein (p21) in established colorectal cell lines and short term cultures of primary colorectal tumour cells was determined by flow cytometry and mutation in the ras gene by sequencing of amplified segments of the gene.Results-The cell lines showed a variation in their modulation of MHC class II antigens and ICAM-1, ranging from no induction to a 98-fold increase in class II antigen expression in the HT29 cell line. Previous work indicated that most tumours could not be induced to express class II antigens. Four of the five least inducible lines either contained mutant ras or highly expressed the oncoprotein. The four highly inducible cell lines all contained non-mutant ras. Of the 21 tumours studied in primary culture, 10 were inducible, one of which contained mutant ras. Of the remaining non-inducible tumours, four were mutant.Conclusions-Correlations between ras activation and failure to respond to IFN-gamma could not be shown to be significant. Therefore, ras activation, and concomitant subversion of intracellular signalling pathways, is probably not the major determinant in failure to activate class II antigens and ICAM-1.

KRAS Mutation and Consensus Molecular Subtypes 2 and 3 Are Independently Associated with Reduced Immune Infiltration and Reactivity in Colorectal Cancer

“…At the protein level, around 50% of both RAS MT and RAS WT CRC samples were completely negative for class II expression by IHC and only 6.4% RAS MT tumours had >50% class II positive cells (Supp Figs 1 C-D and 2 F-H; Table 1). When class II protein expression was analysed in the cancer samples that had detectable expression of class II [i.e., excluding the class II negative cases in which transcriptional silencing of CIITA would prevent IFNγ inducibility via STAT1 (30,31)], we found that RAS mutation was associated with reduced class II expression on the cancer cells (RAS MT class II expressing CRC median epithelial class II H-score = 136.14, RAS WT median = 168.33, Mann-Whitney U p = 0.01) with no differences in stromal class II expression (RAS MT CRC stromal median = 146.96, RAS WT median = 141.56, Mann-Whitney U p = 0.16).…”

“…However, CIITA expression was suppressed in this data set, which would likely mask any KRAS MT-mediated STAT1 impact. Transcriptional repression of CIITA is seen in a proportion of CRC samples (30) as is the complete failure of IFNγ to induce class II expression in half of primary CRC cells (31). Both of these effects are RAS-independent.…”

Identification of Factors Affecting Organizational Silence from the Viewpoint of Middle Managers of Shiraz University of Medical Sciences: A Qualitative Study

“…The twentieth century is known as the age of "knowledge economy", which is the result of creativity and innovation (1). Organizations are in a constant struggle to maintain competitive advantages through creativity development, therefore they allow the development of new ideas in employees (2), the main sources of creativity and innovation in organizations.…”