title: Dissociation of ras oncogene-induced gene expression and anchorage-independent growth in a series of somatic cell mutants.
abstract: The mechanism or mechanisms by which ras oncogenes induce morphological transformation and anchorage-independent growth are poorly understood but are thought to involve stable alterations in gene expression. We previously described a genetically dominant, mutant rat fibroblast cell line (ER-1-2) that is resistant to ras-induced anchorage-independent growth. We now describe a cell line derived from ER-1-2 cells, termed ER-1-2T, that has apparently sustained a second, dominant mutation that conferred on these cells the ability to form colonies in soft agar. Analysis of these and control cell lines demonstrated that deregulation of many of the genes commonly associated with the transformed phenotype could be dissociated from anchorage-independent growth. After infection with a ras-expressing retrovirus, both control and ER-1-2 cell lines constitutively expressed elevated levels of the c-jun, junB, fosB, c-myc, collagenase, ornithine decarboxylase, osteopontin, stromelysin, cathepsin L, and insulin-like growth factor 1 genes. These data indicate that signaling events downstream of ras were largely intact in ER-1-2 cells and that the defect in these cells lies either on a pathway separate from those that control stable, ras-mediated expression of these genes or at a point in the cell-division cycle distinct from those that control expression of the genes. In contrast, only c-jun, junB, c-myc, and ornithine decarboxylase were expressed at a significantly elevated level in ER-1-2T cells. Thus, deregulated expression of the genes analyzed was not sufficient for anchorage-independent growth. Furthermore, deregulation of most of them was also not necessary.
authors.affiliation: Department of Biochemistry, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Feinleib
authors.forename: R S
authors.initials: RS
authors.lastname: Krauss
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D015972:Gene Expression Regulation, Neoplastic; D017781:Genes, Immediate-Early; D011905:Genes, ras; D006822:Hybrid Cells; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats
chemical_list: D011493:Protein Kinase C