Cloning and characterization of UROC28, a novel gene overexpressed in prostate, breast, and bladder cancers

A novel gene, designated UROC28, was identified by an agarose gel-based dif ferential display technique, and it was found to be up-regulated in prostat e, breast, and bladder cancer. Expression of UROC28 was also up-regulated i n prostate cancer cells in the presence of androgens as demonstrated by rel ative quantitative reverse transcription-PCR, The elevated expression of th is gene was observed to increase in surgically removed tissues concomitantl y with rising Gleason grade and was most elevated in metastatic tissue. URO C28 protein was detected in serum by Western slot blot analyses, and a sign ificant higher UROC28 protein level was found in sera of prostate cancer in dividuals compared with normal individuals and individuals with nonmalignan t prostatic hyperplasia. Northern analyses in normal tissues showed that th e UROC28 cDNA hybridizes to two mRNAs at about 2.1 and 2.5 kb. Nucleic acid sequence analyses indicated that these two alternatively spliced mRNA vari ants differ only at the 3' untranslated region. These two mRNAs encode the same protein with 135 amino acids. Bioinformation analyses suggest that the re is a possible transmembrane domain from amino acid aa34 to aa50, three p rotein kinase-C phosphorylation sites at aa62 (SQK), aa89 (TMK), and aa94 ( SMK), and one myristylation site at aa118 (GLECCL). Genomic Southern hybrid ization and chromosomal mapping demonstrated that UROC28 is encoded by a si ngle copy of gene at chromosome 6q23-24. Iri situ hybridization and immunoh istochemistry experiments further confirmed up-regulation of this gene in p rostate and breast cancers with the expression localizing to the glandular epithelium. This gene did not demonstrate increased expression in lung and colon cancer tissues.