The TMPRSS2 gene encoding transmembrane serine protease is overexpressed in a majority of prostate cancer patients: detection of mutated TMPRSS2 form in a case of aggressive disease.
The serine protease TMPRSS2 gene expression was studied by in situ hybridization using benign prostatic hyperplasia and prostate cancer tissue samples from 32 patients. Expression of TMPRSS2 gene was higher in cancer cells than that in benign cells in 84% of the specimens containing both benign and malignant tissues. The TMPRSS2 mRNA level was significantly increased in poorly differentiated (p = 0.014, n = 7) and untreated (p = 0.022, n = 13) primary prostate adenocarcinomas compared to benign tissues. In addition, androgen-deprivation therapy significantly decreased the expression of TMPRSS2 in benign prostate tissue (p = 0.07), which is in accordance with the androgen-inducible expression of the gene. The gene copy number of TMPRSS2, analyzed by competitively differential PCR, was duplicated in the malignant cells of about 38% of the prostate cancer patients analyzed. Thus, the increase in the gene copy number is probably not the primary reason for the detected overexpression of the TMPRSS2 gene. Mutations in the TMPRSS2 gene were screened using DNA isolated from paraffin-embedded prostate cancer tissues from 9 patients with aggressive prostate cancer and from 9 patients with nonaggressive disease. Thirteen exons covering the coding region were checked using enzymatic mutation detection and direct sequencing. One patient with aggressive prostate cancer carried a deletion and a stop codon in exon 11, leading to inactivation of the serine protease domain in TMPRSS2.
Vaarala
M H
MH
Biocenter Oulu and World Health Organization Collaborating Centre for Research on Reproductive Health, University of Oulu, Oulu, Finland.
Porvari
K
K
Kyllönen
A
A
Lukkarinen
O
O
Vihko
P
P
D006801:Humans; D008297:Male; D009154:Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics*; D012697:Serine Endopeptidases / Q000235:genetics*
D012697:Serine Endopeptidases; C421305:TMPRSS2 protein, human