Characterization of the TMPRSS2 Protease as a Modulator of Prostate Cancer Metastasis

摘要

TMPRSS2 is a Type II transmembrane serine protease (TTSP) regulated by androgenic hormones and is expressed preferentially in the human prostate. Although the functional role of this enzyme remains unclear, interest in such a serine protease stems from observations of its clinical implication in prostate cancer, as emerging evidence indicates increased TMPRSS2 expression in prostate carcinoma. To determine the relevance and consequence of TMPRSS2 overexpression in prostate cancer development, we generated four transgenic mouse models that overexpress human or mouse, wild type or mutant forms of TMPRSS2. We have determined that the transgenic lines have significantly increased expression of the target genes, with hrGFP as a transgene marker clearly visible in the ventral lobes while HA expression is detected in all of the prostate lobes. Although enhanced TMPRSS2 expression does not affect mouse fertility, we observed disorganization and disruption of the basement membrane. These findings suggest a mechanism by which TMPRSS2 contributes to primary prostate cancer progression and promotes metastasis.