Evaluation of role of angiotensin III and aminopeptidases in prostate cancer cells.
BACKGROUND
The aim of this study was to perform a comprehensive evaluation of angiotensin III (Ang-III) and related converting enzymes, aminopeptidase A (APA) and N (APN), in prostate cancer.


METHODS
We investigated the effects of Ang-III on the in vitro growth of human prostate cancer cells and the expression of APA and APN in cells treated with Ang-III or hormonal agents. Furthermore, we performed real-time quantitative PCR to investigate the expression pattern of APA and APN in 86 prostate tissue samples including normal prostate, untreated and hormone refractory prostate cancer (HRPC).


RESULTS
Ang-III stimulated cell proliferation, and the proliferative effect was inhibited by olmesartan, an AT(1) receptor blocker (ARB). Western blot analysis showed that phosphorylation of mitogen-activated protein kinase (MAPK) was enhanced by Ang-III and inhibited by olmesartan. APN mRNA level in HRPC was significantly lower than that in normal prostate and untreated prostate cancer tissue. In LNCaP cells, APN expression was augmented by Ang-III, whereas APA expression was not modulated. Hormonal agents, such as estradiol (E2) and dexamethasone (Dex), enhanced APA expression, but did not modulate APN expression in LNCaP cells.


CONCLUSIONS
Our results suggest that Ang-III and related converting enzymes contribute to cell proliferation of prostate cancer, and may be implicated in cancer progression.
Teranishi
Jun-ichi
J
Department of Urology, Yokohama City University Medical Center, Minami-ku, Yokohama, Japan.
Ishiguro
Hitoshi
H
Hoshino
Koji
K
Noguchi
Kazumi
K
Kubota
Yoshinobu
Y
Uemura
Hiroji
H
D000805:Angiotensin III / Q000378:metabolism* / Q000494:pharmacology; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D018826:CD13 Antigens / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D043384:Glutamyl Aminopeptidase / Q000378:metabolism*; D006801:Humans; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism
D018931:Antineoplastic Agents, Hormonal; D012333:RNA, Messenger; D000805:Angiotensin III; D004958:Estradiol; D003907:Dexamethasone; D020928:Mitogen-Activated Protein Kinases; D018826:CD13 Antigens; D043384:Glutamyl Aminopeptidase