%0 Journal Article
%T Alterations in LMTK2, MSMB and HNF1B gene expression are associated with the development of prostate cancer
%A Lorna W Harries
%A John RB Perry
%A Paul McCullagh
%A Malcolm Crundwell
%J BMC Cancer
%D 2010
%I BioMed Central
%R 10.1186/1471-2407-10-315
%X We measured the expression and isoform usage of seven prostate cancer candidate genes in benign and malignant prostate by real-time PCR, and correlated these factors with cancer status and genotype at the GWAS risk variants.We determined that levels of LMTK2 transcripts in prostate adenocarcinomas were only 32% of those in benign tissues (p = 3.2 กม 10-7), and that an independent effect of genotype at variant rs6465657 on LMTK2 expression in benign (n = 39) and malignant tissues (n = 21) was also evident (P = 0.002). We also identified that whilst HNF1B(C) and MSMB2 comprised the predominant isoforms in benign tissues (90% and 98% of total HNF1B or MSMB expression), HNF1B(B) and MSMB1 were predominant in malignant tissue (95% and 96% of total HNF1B or MSMB expression; P = 1.7 กม 10-7 and 4 กม 10-4 respectively), indicating major shifts in isoform usage.Our results indicate that the amount or nature of mRNA transcripts expressed from the LMTK2, HNF1B and MSMB candidate genes is altered in prostate cancer, and provides further evidence for a role for these genes in this disorder. The alterations in isoform usage we detect highlights the potential importance of alternative mRNA processing and moderation of mRNA stability as potentially important disease mechanisms.Cancer of the prostate is the most common male malignancy in the Western world, accounting for 25% of all male UK cancers (taken from http://info.cancerresearchuk.org/cancerstats webcite). Although survival rates are increasing, cancer of the prostate remains the second most common cause of cancer death in UK men after lung cancer. Several risk factors have been identified, the main factors being age [1], family history [2] and ethnic origin [3]. Prostate cancer is uncommon in men under 50 years old, but 80% of men aged over 80 years were found to have cancerous cells in their prostate at the time of death [1]. Estimates suggest that between 30 - 40% of all early onset cases of prostate cancer (< 55yrs) are caus
%U http://www.biomedcentral.com/1471-2407/10/315