The effect of eicosanoids on the expression of MHC genes in cultured human colon cancer cells and mouse colonocytes in vivo.
Eicosanoids have been implicated in the pathogenesis of cancer and are known to regulate the expression of antigens of the major histocompatibility complex (MHC). In human colon cancer, we have recently observed that: (a) the expression of MHC class I and II antigens are markedly reduced; and (b) the levels of PGE2, but not of PGF2 alpha and LTB4, are elevated compared to histologically normal mucosa. Therefore, we investigated the effect of PGE2, PGF2 alpha and LTB4 on the regulation of MHC class I antigens in two human colon adenocarcinoma cell lines and in a murine model of colon cancer. None of these eicosanoids had any significant effect on the expression of MHC class I antigens in the human colonocytes or the transcription rate of class I genes, with the exception of LTB4 which only modestly suppressed the transcription rate. Similarly, 16, 16-dimethyl-PGE2 had no effect on the expression of MHC class I genes in the colonocytes of BALB/c mice treated with the carcinogen dimethylhydrazine. We conclude that PGE2, PGF2 alpha and LTB4 did not affect the expression of MHC class I antigens in cultured human colon adenocarcinoma cells, and 16, 16-dimethyl PGE2 did not affect their expression in mice, even when mice were treated with a colon carcinogen. Thus, these eicosanoids are an unlikely regulator of the observed underexpression of MHC class I antigens in human colon cancer.
Feng
Y
Y
Department of Medicine, Cornell University Medical College, New York, NY 10021, USA.
Papavassiliou
E D
ED
Arvind
P
P
Tsioulias
G J
GJ
Rigas
B
B
D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology; D000230:Adenocarcinoma / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D000818:Animals; D003106:Colon / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D015237:Dinoprost / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D015777:Eicosanoids / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005805:Genes, MHC Class I; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D007975:Leukotriene B4 / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D014407:Tumor Cells, Cultured
D015777:Eicosanoids; D015395:Histocompatibility Antigens Class I; D007975:Leukotriene B4; D015237:Dinoprost; D015232:Dinoprostone; D015064:16,16-Dimethylprostaglandin E2