P16 GENE OVEREXPRESSION IN MOUSE BLADDER CARCINOMAS

Deletion of 9p21 has frequently been observed in human bladder carcino mas. A candidate target suppressor gene, p16, was recently identified within this deleted region. In this study, we therefore investigated t he loss of heterozygosity (LOH) of the p16 gene which is located on mo use chromosome 4, as well as its expression in mouse bladder carcinoma s. We also studied the effects of normal cell contamination on LOH ana lysis using xenografts in CD-1(ICR) nude mice from B6C3F1 bladder carc inomas. We could not detect any LOH at the p16 locus in the mouse prim ary bladder carcinomas and xenografts. Surprisingly, overexpression of p16 was found in all primary mouse bladder carcinomas. Using microsat ellite polymorphisms, a distinction could be made between PCR products derived from B6C3F1 and CD-1(ICR) nude mice. It was thereby confirmed that effects of normal cell contamination on LOH analysis are negligi ble when only tumor tissue is carefully sampled. The results suggest t hat abnormalities of p16 expression may be involved in mouse bladder c arcinogenesis, but that gene deletion is not involved. (C) 1998 Elsevi er Science Ireland Ltd.