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Cell‐specific effects of RAS oncogene and protein kinase C agonist TPA on P‐glycoprotein function
Author(s) -
Stromskaya T.P.,
Grigorian I.A.,
Ossovskaya V.S.,
Rybalkina E.Y.,
Chumakov P.M.,
Kopnin B.P.
Publication year - 1995
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(95)00662-s
Subject(s) - protein kinase c , oncogene , microbiology and biotechnology , k562 cells , agonist , cell culture , biology , flow cytometry , p glycoprotein , cytotoxic t cell , cancer research , receptor , chemistry , cell , signal transduction , in vitro , biochemistry , cell cycle , genetics , multiple drug resistance , antibiotics
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.