Prostate cancers generally acquire an
androgen-independent growth capacity with progression, resulting in resistance to
antiandrogen therapy. Therefore, identification of the genes regulated through this process may be important for understanding the mechanisms of prostate
carcinogenesis. We here utilized
androgen-dependent/independent transplantable
tumors, newly established with the 'transgenic rat
adenocarcinoma in prostate' (TRAP) model, to analyze their gene expression using microarrays. Among the overexpressed genes in
androgen-independent
prostate cancers compared with the
androgen-dependent
tumors,
glutathione S-transferase pi (GST-pi) was included. In line with this, human
prostate cancer cell lines PC3 and DU145 (
androgen independent) had higher expression of GST-pi compared with LNCaP (
androgen dependent) as determined by semiquantitative reverse transcription-polymerase chain reaction analysis. To investigate the roles of GST-pi expression in
androgen-independent human
prostate cancers, GST-pi was knocked down by a
small interfering RNA (
siRNA), resulting in significant decrease of the proliferation rate in the
androgen-independent PC3 cell line. In vivo, administration of GST-pi
siRNA-
atelocollagen complex decreased GST-pi
protein expression, resulting in enhanced numbers of TdT mediated dUTP-
biotin nick-end labering (TUNEL)-positive apoptotic cells. These findings suggest that GST-pi might play important roles in proliferation of
androgen-independent human
prostate cancer cells.