A role for myn in Ha-ras transformation of mouse 10T1/2 fibroblasts.
The human max protein has been shown to form heterodimers with myc family proteins. The ability of myc+max heterodimers to act as sequence-specific transcriptional activators appears to be essential for the oncogenic activity of myc. max (also called myn in murine cells) can homodimerize to form a transcriptionally inactive complex. We previously showed that in mouse 10T1/2 cells, a combination of activated ras, c-myc, and a mutant form of p53 can cooperate in the induction of cellular transformation and metastasis. In the study presented here, we tested the hypothesis that expression of the myn gene may play a role in this cooperative process. Analysis of myn mRNA in these cell lines revealed the presence of a major 2.0-kb RNA species. This message and the 21- and 22-kDa myn polypeptides it encodes were significantly overexpressed in cells transformed by activated ras alone, by ras in combination with c-myc or mutant p53, or by ras plus myc plus mutant p53, in comparison with untransformed parental 10T1/2 cells. We also found that induction of ras expression in a cell line harboring an inducible ras gene was accompanied by an increase in myn mRNA expression. Interestingly, cotransfection of 10T1/2 cells with ras and myn inhibited cellular transformation in a focus-forming assay when compared with transfection with ras alone. These results suggest a role for ras in the regulation of myn gene expression and suggest a model of oncogene cooperativity in which the relative levels of myc and myn gene expression can influence ras transformation of mouse 10T1/2 cells.
Taylor
W R
WR
Manitoba Institute of Cell Biology, University of Manitoba, Winnipeg, Canada.
Wright
J A
JA
D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000235:genetics*; D015870:Gene Expression; D016259:Genes, myc; D016158:Genes, p53; D011905:Genes, ras; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000235:genetics; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000235:genetics
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C068422:Max protein, mouse