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Organ specific Gst‐pi expression of the metastatic androgen independent prostate cancer cells in nude mice
Author(s) -
Naiki Taku,
Asamoto Makoto,
ToyodaHokaiwado Naomi,
NaikiIto Aya,
Tozawa Keiichi,
Kohri Kenjiro,
Takahashi Satoru,
Shirai Tomoyuki
Publication year - 2012
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.21455
Subject(s) - prostate cancer , prostate , metastasis , cancer research , medicine , carcinogenesis , adenocarcinoma , androgen , transplantation , pathology , cancer , hormone
BACKGROUND Elucidating the mechanisms of metastasis in prostate cancer, particularly to the bone, is a major issue for treatment of this malignancy. We previously reported that an androgen‐independent variant had higher expression of glutathione S‐transferase pi (Gst‐pi) compared with a parent androgen‐dependent transplantable rat prostate carcinoma which was established from the transgenic rat for adenocarcinoma of the prostate (TRAP). METHODS A new cell line, PCai1, was established from the androgen‐independent tumor and investigated its metastatic potential in nude mice. The tumorigenesis of PCai1 cells in vivo was studied by subcutaneous transplantations into nude mice. The growth in the microenvironment of the prostate was studied by orthotopic transplantation of PCai1 cells into nude mice. The metastatic potential of PCai1 cells was studied by tail vein injections. Effects of Gst‐pi knocked down were analysis in PCai1 cells. RESULTS PCai1 frequently formed metastatic lesions in the lung and lymph nodes after orthotopic implantation in the prostate. Intravenous injections of PCai1, metastasis to lung and bone were obvious. PCai1 had strong expression for Gst‐pi, therefore we tried knocked down Gst‐pi . Gst‐pi ‐siRNA in vitro significantly suppressed cell proliferation rate. In addition, high levels of intracellular reactive oxygen species (ROS) were recognized in the Gst‐pi knockout. CONCLUSIONS Gst‐pi expression of the prostate cancers are dependent on metastatic site, and that Gst‐pi has an important role in adapting prostate cancer for growth and metastasis involving an alteration of ROS signals. Prostate 72:533–541, 2012. © 2011 Wiley Periodicals, Inc.