Cell-specific effects of RAS oncogene and protein kinase C agonist TPA on P-glycoprotein function.
We compared the influence of exogenous N-ras oncogene and treatment with PKC agonist 12-O-tetradecanoylphorbol-13-acetate (TPA) on P-glycoprotein (Pgp) function in various human, rat and dog cell lines. Two approaches were used: (a) flow cytometry analysis of Rhodamine 123 (Rh123) exclusion; and (b) sensitivity to cytotoxic action of colchicine. We have found that in Rat1 fibroblasts, rat IAR2 epithelial cells and rat McA RH 7777 (hepatoma), ras activates Pgp function, while in MDCK (dog kidney), K562 (human chronic myelogenous leukaemia) and LIM1215 (human colon carcinoma) cells it either has no effect or even acts in opposite direction. TPA-induced Pgp function shows dissimilar pattern of cell specificity. It is assumed that PKC and ras oncogene regulate mdr1 gene expression through at least partially distinct signalling pathways.
Stromskaya
T P
TP
Institute of Cancerogenesis, Cancer Research Center, Moscow, Russian Federation.
Grigorian
I A
IA
Ossovskaya
V S
VS
Rybalkina
E Y
EY
Chumakov
P M
PM
Kopnin
B P
BP
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D003078:Colchicine / Q000494:pharmacology; D004285:Dogs; D018432:Drug Resistance, Multiple; D005786:Gene Expression Regulation / Q000187:drug effects; D011905:Genes, ras / Q000235:genetics / Q000502:physiology*; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D011493:Protein Kinase C / Q000819:agonists*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D012190:Retroviridae / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D012333:RNA, Messenger; D014700:Verapamil; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D003078:Colchicine