Codeletion of the JUN proto-oncogene and the CDKN2A tumor-suppressor gene in HRAS-transformed rat embryo fibroblast cell lines
✍ Scribed by Jian-Nian Zhou; Sofia Ljungdahl; Dan Röhme; Göran Levan; Maria C. Shoshan; Stig Linder
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- English
- Weight
- 181 KB
- Volume
- 20
- Category
- Article
- ISSN
- 1045-2257
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✦ Synopsis
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 HRAS VAL12 . 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.