Alterations in LMTK2, MSMB and HNF1B gene expression are associated with the development of prostate cancer.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
BACKGROUND: Genome wide association studies (GWAS) have identified several genetic variants that are associated with prostate cancer. Most of these variants, like other GWAS association signals, are located in non-coding regions of potential candidate genes, and thus could act at the level of the mRNA transcript. METHODS: 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. RESULTS: We determined that levels of LMTK2 transcripts in prostate adenocarcinomas were only 32% of those in benign tissues (p = 3.2 x 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 x 10(-7) and 4 x 10(-4) respectively), indicating major shifts in isoform usage. CONCLUSIONS: 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.
Northcott Devon Medical Foundation
Research Support, Non-U.S. Gov't
Copyright © 2010 Harries et al; licensee BioMed Central Ltd.
Vol. 10, pp. 315 -
Place of publication
Showing items related by title, author, creator and subject.
The androgen receptor controls expression of the cancer-associated sTn antigen and cell adhesion through induction of ST6GalNAc1 in prostate cancer. Munkley, J; Oltean, S; Vodák, D; Wilson, BT; Livermore, KE; Zhou, Y; Star, E; Floros, VI; Johannessen, B; Knight, B; McCullagh, P; McGrath, J; Crundwell, M; Skotheim, RI; Robson, CN; Leung, HY; Harries, LW; Rajan, P; Mills, IG; Elliott, DJ (Impact Journals, 2015-10-07)Patterns of glycosylation are important in cancer, but the molecular mechanisms that drive changes are often poorly understood. The androgen receptor drives prostate cancer (PCa) development and progression to lethal ...
Hamilton, W; Vedsted, P (Royal College of General Practitioners, 2011-11)Editorial
Risk of cancer in first seven years after metal-on-metal hip replacement compared with other bearings and general population: linkage study between the National Joint Registry of England and Wales and hospital episode statistics. Smith, AJ; Dieppe, P; Porter, M; Blom, AW; National Joint Registry of England and Wales (BMJ Publishing Group, 2012)To determine whether use of metal-on-metal bearing surfaces is associated with an increased risk of a diagnosis of cancer in the early years after total hip replacement and specifically with an increase in malignant melanoma ...