mRNA levels and enzyme activities of protein phosphatases in drug-resistant rat ascites hepatomas.
mRNA levels and enzyme activities of the serine/threonine protein phosphatases (EC 3.1.3.16) type 1 (PP1) and 2A (PP2A) in drug-resistant rat ascites hepatoma cells were examined and compared with those in the parental drug-sensitive cell lines, under drug-free conditions. The mRNA levels of PP1 alpha were much higher in all the hepatomas, either sensitive or resistant, compared with normal liver. The mRNA level of PP2C alpha was decreased in the drug-resistant hepatomas compared with the parental drug-sensitive hepatomas, whereas mRNA levels of PP1 alpha, PP1 gamma 1 and PP2A alpha in resistant hepatomas showed diverse deviations, which are not drug-resistance-specific. However, both spontaneous and potential PP1 activities in particulate fractions of the resistant hepatomas were markedly increased compared with those of the sensitive hepatomas and normal rat liver. Western blot analysis showed that the resistant hepatomas contained larger amounts of PP1 alpha in both cytosolic and particulate fractions than the sensitive hepatomas and rat liver. In both groups of hepatomas, spontaneous and potential activities of PP2A were kept lower than those in normal rat liver, but there was no difference between drug-sensitive and -resistant hepatomas. These results suggest an involvement of PP1 in development of drug-resistant phenotype.
Saadat
M
M
Section of Biochemistry, Hokkaido University, Japan.
Saeki
H
H
Kudo
T
T
Mizuno
Y
Y
Kikuchi
K
K
D000818:Animals; D015153:Blotting, Western; D003600:Cytosol / Q000201:enzymology; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000096:biosynthesis / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D010749:Phosphoprotein Phosphatases