Human p57(KIP2) defines a new imprinted domain on chromosome 11p but is not a tumour suppressor gene in Wilms tumour

Abstract

Mouse p57(Kip2) arrests cells in G1 by functioning as a strong inhibitor of several G1 cyclin/Cdk complexes. Human p57(KIP2) has been suggested to be a tumour suppressor gene because of its location at 11p15.5 which frequently undergoes maternal allele LOH in several types of cancer. This suggestion was supported by the discovery that mouse p57(Kip2) is imprinted with expression from only the maternally inherited allele. Interestingly, p57(KIP2) is several hundred kilobases from the imprinted H19 and IGF2 genes which are involved in growth regulation. Here we show that human p57(KIP2) is imprinted with expression from the maternal allele. However, unlike the mouse, the imprinting is incomplete with significant expression from the paternal allele depending on the tissue examined. We have also shown that the imprinting of p57KIP2 occurs independently of the H19/IGF2 domain and thus there must be at least two imprinted domains in 11p15.5. Finally, by examining Wilms tumours we have shown that following maternal 11p LOH, p57(KIP2) was expressed from the paternal allele. Therefore, p57KIP2 cannot function as an imprinted tumour suppressor gene, at least in Wilms tumour.