PRR5 encodes a conserved proline-rich protein predominant in kidney: analysis of genomic organization, expression, and mutation status in breast and colorectal carcinomas

Loss of heterozygosity on chromosome 22q13.31 is a frequent event during human breast and colorectal carcinogenesis. Herein we characterize a novel gene at chromosome 22q13.31 designated PRR5. Alternative promoter usage and splicing converge to generate five PRR5 transcript variants with maximum mRNA expression in kidney. In vitro transcription/translation demonstrated that the five variants generate three protein isoforms differing in their N-terminal length. Mutational analysis of PRR5 in human breast and colorectal tumors did not reveal somatic mutations. However, mRNA expression analyses revealed PRR5 overexpression in a majority of colorectal tumors but substantial downregulation of PRR5 expression in a subset of breast tumors and reduced expression in two breast Cancer cell lines. Treatment with trichostatin A increased PRR5 mRNA levels in BT549 and MDA-MB-231 cells, whereas 5'-aza-2'-deoxycytidine induced expression in MDA-MB-231 cells only. Thus, PRR5 may represent a potential candidate tumor suppressor gene in breast Cancer.