Cell‐specific effects of RAS oncogene and protein kinase C agonist TPA on P‐glycoprotein function

FEBS Letters

Rybalkina, E.Y.²  Chumakov, P.M.¹  Kopnin, B.P.²  Stromskaya, T.P.²  Ossovskaya, V.S.¹  Grigorian, I.A.² 

[1] Engelhardt Institute of Molecular Biology, Moscow, Russian Federation;Institute of Cancerogenesis, Cancer Research Center, Kashirskoye shosse 24, Moscow, 115478, Russian Federation

关键词: RAS oncogene;    Protein kinase C;    Multidrug resistance;    P-glycoprotein;    MDR;    multidrug resistance;    FCM;    flow cytometry;    Pgp;    P-glycoprotein;    PKC;    protein kinase C;    TPA;    12-O-tetradecanoylphorbol-13-acetate;    PBS;    phosphate-buffered saline;    Rh123;    Rhodamine 123;    FCS;    fetal calf serum;    PCR;    polymerase chain reaction;   

DOI  :  10.1016/0014-5793(95)00662-S

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown