Epithelial specific transcriptome map of the human prostate.
Doctoral thesis, UCL (University College London).
The prostate has a zonal anatomy, with differing susceptibilities to disease (benign prostatic hyperplasia originates from the transition zone, prostate cancer largely arises in the peripheral zone). The molecular reasons for this are not understood. Previous prostate cancer microarray studies have used whole benign, diseased or tissue adjacent to the carcinoma as normal controls, for what is an epithelial disease. This study provides a gene expression profile of normal, non-diseased prostate, or a ‘reference prostate gene expression profile’. This has been compared to prostate cancer to identify novel biomarkers of disease. This study also investigates zonal differences in gene expression between different anatomical zones of the prostate. I used normal, human donor prostate tissue, laser capture microdissection (LCM), and Affymetrix gene expression arrays to achieve these aims. Eight LCM prostate epithelial samples from 3 donor prostates were used. The gene expression data was validated by low density real-time PCR and immunohistochemistry on a prostate tissue microarray. Major differences in gene expression were discovered between whole tissue and LCM epithelium only prostate using homology tables. Novel prostate adenocarcinoma genes were identified using a publicly available LCM prostate cancer gene expression array dataset. 9318 genes showed significant differential expression in normal vs. cancer datasets. Three targets, MCM2, NR1D1 and ABCA1 were validated at the protein level. Expression of NR1D1 and ABCA1 were increased in cancer, suggesting they are novel epithelial biomarkers of prostate cancer. An analysis of zonal differences in gene expression found significant differences between zones. Zonal specific markers included TGM4 (central zone), LPL (peripheral zone), and COL9A1 (transition zone). This study provides: (i) a gene expression profile of the normal prostate epithelium (ii) novel, prostate adenocarcinoma specific gene and protein markers and (iii) the first gene expression profile of normal epithelium on the basis of zonal anatomy of the prostate.
|Title:||Epithelial specific transcriptome map of the human prostate|
|Open access status:||An open access version is available from UCL Discovery|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Surgery and Interventional Science (Division of)|
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