Lack of c-jun expression in a transformed cell line isolated by glucocorticoid promotion of ras-transfected rat embryo fibroblasts.
Rat embryo fibroblasts (REFs) are inefficiently transformed by the T24-ras oncogene. A contributing factor to cellular resistance to transformation is the limited tolerance to p21-ras oncoprotein expression. Here we present data suggesting that long-term glucocorticoid treatment of ras oncogene-transfected REFs results in increased tolerance to p21-ras oncoproteins, leading to expression of the transformed phenotype. Stably transformed cell lines that expressed high levels of H-ras and could be maintained in the absence of hormone were isolated. In three out of four lines studied, the AP-1-dependent collagenase gene was expressed at a low level. In one of these lines, low collagenase expression was paralleled by lack of c-jun mRNA. Immunochemical analysis revealed that progression to hormone independence was not paralleled by mutations in the p53 gene. We propose that a decreased expression of AP-1-driven genes may result in increased tolerance to p21-ras oncoprotein.
Marshall
H
H
Department of Oncology, Radiumhemmet, Karolinska Institute and Hospital, Stockholm, Sweden.
Popowicz
P
P
Engel
G
G
Martens
I
I
Linder
S
S
D000818:Animals; D001483:Base Sequence; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D017364:Collagenases / Q000235:genetics; D015870:Gene Expression; D016758:Genes, jun; D011905:Genes, ras; D005938:Glucocorticoids / Q000494:pharmacology*; D008969:Molecular Sequence Data; D010957:Plasmids; D016755:Proto-Oncogene Proteins c-jun / Q000502:physiology*; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000502:physiology; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D005938:Glucocorticoids; D016755:Proto-Oncogene Proteins c-jun; D011965:Receptors, Glucocorticoid; D016159:Tumor Suppressor Protein p53; D017364:Collagenases