Expression of p19(INK4d), CDK4, CDK6 in glioblastoma multiforme

Abstract

Deregulation of the G1/S checkpoint is a frequent event in the development of glioblastoma multiforme (GBM). Previous studies have shown more than 50% of primary GBM tumours contain either complete loss of the p16(INK4a) locus or amplification of the CDK4 gene. Moreover, many heterozygosity studies have shown deletion on human chromosome 19p13.2, where the p19(INK4d) gene has been localized. We examined the expression of p19(INK4d) and its two CDK substrates in a series of glioma-derived cell lines and tumours. No gene rearrangement or deletion was observed in the p19(INK4d) gene in these cell lines; however, expression of CDK4 and CDK6 was elevated relative to matched normal brain tissue in eight of 18 GBM tumours (44%). Furthermore, CDK6 expression level was increased in 12/14 glioblastomas, but undetectable in tumour samples of a previous lower grade tumour from the same patient. These data attest to the functional importance of both CDK4 and CDK6 in astrocytic tumourigenesis, particularly during the later stages of tumour progression.