Evidence of post-translational regulation of P-glycoprotein associated with the expression of a distinctive multiple drug-resistant phenotype in Chinese hamster ovary cells.
Chinese hamster ovary (CHO) cells following exposure to fractionated X-irradiation in vitro dominantly expressed a distinctive multiple drug-resistant phenotype, characterised by resistance to vinca alkaloids, epipodophyllotoxins and colchicine, but not to anthracyclines, together with overexpression of P-glycoprotein (Pgp), but without any concomitant elevation in Pgp mRNA (J Natl Cancer Inst 1990, 82, 607-612; 1992, 85, 48-53). To investigate the mechanism of this Pgp overexpression, Pgp stability ws examined in an X-irradiation pretreated subline and compared with that of two colchicine-selected drug-resistant CHO sublines. These studies revealed a slower turnover of Pgp in the X-irradiated cells (T1/2 > or = 40 h) relative to the drug-selected sublines (T1/2 = 17 h), indicating that Pgp overexpression appears to be differently regulated in these independently-derived resistant sublines. These data add support to our proposal that the development of drug resistance following X-irradiation may arise by a mechanism distinct from that operating after drug selection.
McClean
S
S
Cellular Chemotherapy Laboratory, Imperial Cancer Research Fund, London, U.K.
Hill
B T
BT
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000818:Animals; D016466:CHO Cells / Q000378:metabolism / Q000528:radiation effects; D002352:Carrier Proteins / Q000096:biosynthesis*; D003078:Colchicine / Q000494:pharmacology*; D006224:Cricetinae; D004351:Drug Resistance / Q000235:genetics*; D005786:Gene Expression Regulation; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D011233:Precipitin Tests; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D003078:Colchicine