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438 ARGINASE AS A PROLIFERATIVE DETERMINANT IN PROSTATE CANCER.
  1. M. B. Orkin,
  2. S. M. Mumenthaler,
  3. S. Cederbaum,
  4. W. Grody
  1. Department of Pathology and Laboratory Medicine, UCLA Medical School, Los Angeles, CA

Abstract

Prostate cancer is the most common cancer diagnosed in US men, yet little is known regarding the mechanisms controlling prostatic cell growth. Previous work has shown that arginase II (AII) is expressed at high levels in the normal prostate and at higher levels in prostate tumors. AII is involved in synthesis of polyamines, which are essential for rapidly growing tissues and are found in high levels in prostate cancer. This leads to the hypothesis that increased AII activity may be involved in prostate cancer cell proliferation, through AII's role in the urea cycle, polyamine synthesis, and nitric oxide metabolic pathways. Western blot analysis with anti-AII antibody on normal prostate (PZ-HPV-7) and prostate cancer (LNCaP, PC-3, DU 145) cell lines showed the highest AII levels in LNCaPs, a more differentiated prostate cancer cell line, compared to levels in the less differentiated PC-3 and DU-145 cell lines, and in the normal PZ-HPV-7. To assess whether increasing AII in normal prostate increases cell proliferation, arginase was over-expressed in normal cells by transfecting PZ-HPV-7 with an AII vector containing GFP and the selectable marker blasticidin. To examine whether AII is hormone dependent or independent, LNCaP cultures were treated with charcoal-stripped media for varying periods to facilitate hormone removal. Charcoal-stripped LNCaPs were compared with normal LNCaPs via Western blotting using anti-AII and anti-PSA (prostate-specific antigen) antibodies. PSA antibody confirmed the hormone-stripping, while AII antibody showed AII levels were congruent with and without hormone-stripping, suggesting AII regulation is hormone independent. In conclusion, this work is essential in elucidating prostate cancer mechanisms and may suggest new directions for diagnosis and therapeutic intervention.

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