Disruption of arginase II alters prostate tumor formation in TRAMP mice.
BACKGROUND
Arginase II (AII) is involved in the polyamine synthetic pathway, and elevated levels of expression have been found in a high proportion of prostate cancer samples and patients. However, the biological function of arginase II in prostate cancer still remains to be elucidated. In this study, we utilized the TRAMP mouse prostate cancer model to better understand the contribution of AII on tumor development.


METHODS
AII expression was determined in prostates from TRAMP mice at 23 weeks of age by real-time RT-PCR and Western blot analysis. Additionally, AII expression was disrupted in the TRAMP model by crossbreeding arginase II knockout (AII KO) mice with TRAMP mice in order to generate the TRAMP/AII KO line. In each group, genito-urinary (GU) tract weights were determined and a pathological evaluation of the tumors was completed.


RESULTS
AII expression was only detectable in those mice without the presence of macroscopic tumors; it was also absent in the TRAMP-C2 cell line, which is characteristic of an advanced prostate tumor. Assessment of the GU weights revealed larger average GU weights in the TRAMP/AII KO mice compared to TRAMP mice. Additionally, a greater percentage of more advanced pathology was found in the TRAMP/AII KO group compared to the TRAMP cohort.


CONCLUSIONS
Based on these results, AII deficiency in the TRAMP model seems to accelerate prostate tumor progression, leading to an overall more advanced cancer stage in these mice. These findings support the possibility that prostatic arginase II could be a potentially useful marker of disease progression.
Mumenthaler
Shannon M
SM
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California 90095-1732, USA.
Rozengurt
Nora
N
Livesay
Justin C
JC
Sabaghian
Anahita
A
Cederbaum
Stephen D
SD
Grody
Wayne W
WW
D000230:Adenocarcinoma / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001119:Arginase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D020162:Hyperargininemia; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009376:Neoplasms, Hormone-Dependent / Q000201:enzymology / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D012334:RNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D053219:Receptors, Tumor Necrosis Factor, Member 25 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012334:RNA, Neoplasm; D053219:Receptors, Tumor Necrosis Factor, Member 25; C506034:Tnfrsf25 protein, mouse; C481673:Arg2 protein, mouse; D001119:Arginase