title: Malignant transformation of human skin fibroblasts by two alternative pathways.
abstract: We developed a telomerase-positive, infinite life span human fibroblast cell strain (MSU-1.0) by transfection of a v-MYC oncogene and spontaneous over-expression of transcription factors SP1/SP3. Loss of expression of p14(ALT) and enhanced expression of SPRY2 gave rise to the MSU-1.1 cell strain. Unlike MSU-1.0 cells, the MSU-1.1 cells can be malignantly transformed by expression of N-RAS(LYS61) or H-Ras(v12) oncoproteins (driven by their original promoters) and expression of a SRC-family protein, v-FES. MSU-1.1 cells can also be malignantly transformed by high expression of these RAS oncogenes or the v-K-RAS oncogene. PDGF-B transformed MSU-1.1 cells give rise to benign tumors (fibromas) in athymic mice. A second route to malignant transformation of the MSU-1.1 cells involves loss of functional TP53 protein by carcinogen treatment and loss of expression of wild type p16(INK). These studies indicate 6-8 "hits" are required to activate the oncogenes and inactivate the suppressor genes we identified.
authors: Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824-1302, USA. mccormi1@msu.edu
authors: J Justin
authors: JJ
authors: McCormick
authors: Veronica M
authors: VM
authors: Maher
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D005347:Fibroblasts / Q000473:pathology*; D006801:Humans; D015398:Signal Transduction; D012867:Skin / Q000473:pathology; D025803:Tumor Suppressor Protein p14ARF / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000502:physiology; D018631:ras Proteins / Q000502:physiology; D019061:src-Family Kinases / Q000502:physiology
chemical_list: D025803:Tumor Suppressor Protein p14ARF; D016159:Tumor Suppressor Protein p53; D019061:src-Family Kinases; D018631:ras Proteins