Decreased arginase II expression in androgen-independent prostate cancer cell lines.

B117

The second isoform of arginase (AII) is involved in the biosynthesis of polyamines and the modulation of nitric oxide synthesis (iNOS), which are key aspects of prostate physiology and cell proliferation. Through both RNA and protein analysis, we have shown AII expression to be most prominent in the more differentiated androgen-dependent prostate cancer cell lines (LNCaP, LAPC-4) and the least prominent in the more undifferentiated androgen-independent cell lines (PC3, DU145). It also appears that when AII expression is high, ornithine aminotransferase (OAT) levels are low. The opposite trend is seen in the androgen-independent cell lines which have high OAT expression and very low AII expression. Polyamine measurements show that LNCaP and LAPC-4 cells have high levels of spermine and very low levels of putrescine where PC3 and DU145 cells show the opposite pattern. This suggests that in early stage prostate cancer, AII is the main enzyme producing the ornithine needed for polyamine synthesis; however, as prostate tumors become more undifferentiated and lose their glandular regions where AII is expressed, high OAT expression may be compensating for the lack of AII and in turn producing the ornithine necessary for polyamine production. Recently, we looked at AII levels in a LNCaP-derived androgen-independent cell line, CL-1, and found loss of AII expression compared to the native LNCaP androgen-dependent cell line. In addition, OAT expression is increased in the CL-1 cell line relative to LNCaP cells, which suggests that CL-1 is acting similar to the androgen-independent cell lines, PC3 and DU145, with respect to AII and OAT activity. This discovery demonstrates that loss of AII is an early event in prostate adenocarcinoma and it is differentially expressed in hormone sensitive versus hormone refractory cell lines.