Growth arrest and suppression of tumorigenicity of bladder carcinoma cell lines induced by the P16/CDKN2 (p16INK4A, MTS1) gene and other loci on human chromosome 9
✍ Scribed by Qiang Wu; Laura Possati; Marco Montesi; Francesca Gualandi; Paola Rimessi; Cristina Morelli; Cecilia Trabanelli; Giuseppe Barbanti Brodano
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- French
- Weight
- 889 KB
- Volume
- 65
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Wild
-type P16ICDKNZ MTSI) cDNA, directed by the cytomegalovirus (CMV) immediate early promoter, was transfected into RT4 and RTI I 2 bladder-carcinoma cell lines bearing a mutated endogenous P16ICDKNZ gene and lacking endogenous P 16lCDKN2 respectively. In both cases, only transfected clones with rearranged exogenous P16ICDKNZ cDNA could be grown and propagated in cell culture. This result is reminiscent of transfection of wild-type p53 into cells with a deleted or mutated endogenous gene and suggests that P16/ CDKNZ, over-expressed under control of the strong CMV promoter, induces growth arrest in RT4 and RTl I 2 cells. Transfer of human chromosome 9 to RT4 cells produced RT4/H9 hybrid clones retaining the P16ICDKNZ gene, since in RT4/H9 cell clones Pl6lCDKNZ-gene expression is modulated by the physiological control of chromosomal regulatory sequences. All the RT4/H9 clones lost the entire chromosome 9, except clone 4 and clone 5, which maintained a deleted and an intact chromosome 9 respectively. Loss of several loci in 9 ~2 1 , including P16ICDKN2, in tumors induced in nude mice by clone 4 and clone 5 suggests that P16/CDKN2 or other genes in 9p2I suppress tumorigenicity in bladder-carcinoma cells. Tumors induced by clone 4 and clone 5 show loss of markers in 9q. The regions 9q22.3, 9q32-33 and 9q34.2, which were maintained in the 2 clones and lost in their derived tumors, may contain tumor-suppressor genes relevant in bladder carcinoma. The results of this study suggest that the P16ICDKNZ gene controls growth of bladder-carcinoma cells when it is over-expressed, and may be involved in the development of bladder carcinoma, but other genes in 9p2I and 9q may participate in bladdercancer progression.