Decreased expression of p57(KIP2) mRNA in human bladder cancer

To identify targets of genetic and epigenetic alterations on chromosome 11p 15.5 in human bladder cancer, expression of the imprinted KIP2, IGF2 and H1 9 genes was studied by quantitative RT-PCR in 24 paired samples of urotheli al carcinomas and morphologically normal mucosa obtained by cystectomy, and in bladder carcinoma cell lines. The most frequent alteration in tumour ti ssue was decreased expression of KIP2 identified in 9/24 (37%) specimens. D ecreased IGF2 and H19 mRNA levels were found in five (21%) and three (13%) tumours, respectively. One tumour each overexpressed IGF2 and H19. Loss of H19 expression was only found associated with loss of KIP2 expression, wher eas decreased expression of IGF2 mRNA occurred independently. Almost all bl adder carcinoma cell lines showed significant changes in the expression of at least one gene with diminished expression of KIP2 mRNA as the most frequ ent alteration. IGF2 mRNA levels were diminished in several lines, but incr eased in others. The KIP2 gene could be an important target of genetic and epigenetic alterations in bladder cancer affecting the maternal chromosome 11p15.5. However, reminiscent of the situation in Wilms' tumours, expressio n of the IGF2 gene on the paternal chromosome can also be disturbed in blad der cancers. (C) 2000 Cancer Research Campaign.