Enhanced levels of oleate-dependent and Arf-dependent phospholipase D isoforms in experimental colon cancer.
Phospholipase D (PLD) (EC 3.1.4.4) is one of the intracellar signal transduction enzymes and plays an important role in a variety of cellular functions. In order to clarify the role of PLD in proliferation and tumorigenesis of colon cancer, we investigated the activities of oleate-dependent and ADP-ribosylation factor (Arf)-dependent types of PLD in experimental colon cancer of the rat. We produced colon cancer in Wistar rats by injecting the carcinogen, dimethylhydrazine dihydrochloride (DMH). The control rats were injected with physiological saline. Mucosal scrapings from the colon were homogenized and centrifuged to obtain the microsomal or membrane fraction. We measured the two types of PLD activities in these fractions using the transphosphatidylation reaction. Both oleate-dependent and Arf-dependent PLD activities were significantly higher in the colon cancer tissue than normal colonic mucosa. The mean specific activity of oleate-dependent PLD) in colon cancers was 1.66 +/- 0.75 (SD) nmol/min/mg whereas the value for normal colonic mucosa was 0.18 +/- 0.09 nmol/min/mg (P < 0.01; Mann-Whitney U-test). On the other hand, the mean specific activity of Arf-dependent PLD in colon cancers was 76.36 +/- 29.37 pmol/min/mg whereas the value for normal colonic mucosa was 19.90 +/- 11.97 pmol/min/mg (P < 0.01; Mann-Whitney U-test). These results suggest that PLD is implicated in the proliferation and tumorigenesis of colon cancer. The present study provides the first evidence for the enhanced levels of two types of PLD in colon cancer and raises the possibility that these PLDs can be used as the potential target for the treatment of colon cancer.
Yoshida
M
M
First Department of Internal Medicine, Gunma University School of Medicine, Maebashi, Japan.
Okamura
S
S
Kodaki
T
T
Mori
M
M
Yamashita
S
S
D019813:1,2-Dimethylhydrazine; D020727:ADP-Ribosylation Factors; D000818:Animals; D002273:Carcinogens; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000201:enzymology*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D007527:Isoenzymes / Q000096:biosynthesis / Q000378:metabolism; D008297:Male; D019301:Oleic Acid / Q000494:pharmacology*; D010664:Phenylmethylsulfonyl Fluoride / Q000494:pharmacology; D010739:Phospholipase D / Q000096:biosynthesis / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation
D002273:Carcinogens; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D019301:Oleic Acid; D010664:Phenylmethylsulfonyl Fluoride; D010739:Phospholipase D; D019204:GTP-Binding Proteins; D020727:ADP-Ribosylation Factors; D019813:1,2-Dimethylhydrazine