title: Codeletion of the JUN proto-oncogene and the CDKN2A tumor-suppressor gene in HRAS-transformed rat embryo fibroblast cell lines.
abstract: The cyclin kinase inhibitor p16, encoded by the CDKN2A gene, suppresses the transformation of mouse embryonic fibroblasts by oncogenic RAS. In contrast, the c-JUN transcription factor (a major component of AP-1) has been suggested to be required for RAS transformation of rodent fibroblasts. The CDKN2A gene and the JUN proto-oncogene have both been mapped to rat chromosome band 5q31-33. We here show that both copies of the CDKN2A gene are deleted in four of eight transformed cell lines derived from the transfection of rat embryo fibroblasts (REF) with HRASVAL12. In two cell lines, the homozygous deletions involved a larger area on 5q31-33, which included the JUN proto-oncogene. JUN-defective cells showed high AP-1 binding activity. Both AP-1 binding activity and stromelysin (transin) mRNA expression were found to be RAS-dependent in one of the JUN-defective cell lines. The finding of deletions of the CDKN2A gene in RAS-transformed REF cell lines is consistent with the concept that CDKN2A suppresses transformation by RAS. The occasional concomitant loss of the adjacent JUN proto-oncogene does not prevent establishment of transformed and tumorigenic cell lines.
authors.affiliation: Department of Oncology and Pathology, Karolinska Institute and Hospital, Stockholm, Sweden.
authors.forename: J N
authors.initials: JN
authors.lastname: Zhou
authors.forename: S
authors.initials: S
authors.lastname: Ljungdahl
authors.forename: D
authors.initials: D
authors.lastname: Röhme
authors.forename: G
authors.initials: G
authors.lastname: Levan
authors.forename: M C
authors.initials: MC
authors.lastname: Shoshan
authors.forename: S
authors.initials: S
authors.lastname: Linder
mesh_terms: D000818:Animals; D015139:Blotting, Southern; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics*; D002461:Cell Line, Transformed; D002872:Chromosome Deletion; D019941:Cyclin-Dependent Kinase Inhibitor p16; D005347:Fibroblasts; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D016758:Genes, jun / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics*; D007621:Karyotyping; D018895:Microsatellite Repeats; D016133:Polymerase Chain Reaction; D051381:Rats
chemical_list: D002352:Carrier Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16