Autocrine induction of major histocompatibility complex class I antigen expression results from induction of beta interferon in oncogene-transformed BALB/c-3T3 cells.
By varying growth conditions, we identified a novel mechanism of autocrine regulation of major histocompatibility complex (MHC) class I gene expression by induction of beta interferon gene expression in transformed BALB/c-3T3 cells. Low-serum conditions enhanced MHC class I antigen expression in v-rasKi- and v-mos-transformed BALB/c-3T3 cells but not in untransformed BALB/c-3T3 cells. Transformed and untransformed cells grown under standard serum conditions (10% bovine calf serum) expressed similar cell surface levels of MHC class I antigens. However, low-serum conditions (0.5% bovine calf serum) induced four- to ninefold increases in cell surface levels of MHC class I antigens in both v-rasKi- and v-mos-transformed cells but not in untransformed cells. These increases in MHC class I gene expression were seen at both the mRNA and cell surface protein levels and involved not only the heavy-chain component of the class I antigens but also beta 2 microglobulin. Beta 1 interferon mRNA and beta interferon-inducible 2',5'-oligoadenylate synthetase mRNA were induced by growth under low-serum conditions in transformed BALB/c-3T3 cells, and antibodies to beta interferon blocked the induction of MHC class I antigen expression by serum deprivation in these cells. These results demonstrate that growth under low-serum conditions leads to induction of beta interferon expression in oncogene-transformed cells which then directly mediates autocrine enhancement of MHC class I gene expression.
Offermann
M K
MK
Division of Medicine, Dana Farber Cancer Institute, Children's Hospital, Boston, Massachusetts 02115.
Faller
D V
DV
D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics; D000818:Animals; D002471:Cell Transformation, Neoplastic; D003470:Culture Media; D005786:Gene Expression Regulation; D005805:Genes, MHC Class I; D006183:H-2 Antigens / Q000235:genetics; D007370:Interferon Type I / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D051379:Mice; D009857:Oncogenes; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D001613:beta 2-Microglobulin / Q000235:genetics
D003470:Culture Media; D006183:H-2 Antigens; D007370:Interferon Type I; D012333:RNA, Messenger; D001613:beta 2-Microglobulin; D015088:2',5'-Oligoadenylate Synthetase