The role of HRK gene in human cancer.

Apoptosis regulators play one of the most critical roles in tumorigenesis, and an imbalance between cell proliferation and apoptosis may contribute to tumor progression. HRK was itself originally identified as a proapoptotic gene induced by diminished levels of cytokine in hematopoietic cells and cultured neurons and repressed by the expression of death-repressor proteins. A few analyses of HRK protein expression in primary central nervous system lymphomas have been performed, and little is known about the epigenetic or post-transcriptional mechanisms that may participate in HRK inactivation. Here we show the data on the 5'-CpG methylation status, loss of heterozygosity on 12q13.1 and its association with HRK expression in human malignancies, including prostate cancers, astrocytic tumors and primary central nervous system lymphomas. Aberrant methylation of CpG islands within the promoter is an epigenetic event largely responsible for the silencing of the HRK gene and subsequent low apoptotic counts in our series of malignancies. Inactivation of HRK apparently occurs in a substantial proportion of all tumor phenotypes and, as a potential proapoptotic gene, HRK may contribute to the development and progression of many human cancers.