TY - JOUR
T1 - Taxol resistance mediated by transfection of the liver-specific sister gene of P-glycoprotein
AU - Childs, Sarah
AU - Yeh, Richard Lin
AU - Hui, David
AU - Ling, Victor
N1 - Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 1998/9/15
Y1 - 1998/9/15
N2 - The sister gene of P-glycoprotein (Spgp) is a liver-specific ATP- binding cassette protein highly related to the P-glycoprotein (Pgp) family (S. Childs et al., Cancer Res., 55: 2029-2034, 1995). Spgp appears to be related to the Pgp family by an ancient duplication occurring before the division of fish and mammals. P-Glycoproteins have diverse functions including broad specificity multidrug resistance in cell lines and tumors, detoxification of tissues such as the intestine and blood-brain barrier, and phosphatidylcholine transport in liver. Spgp is a M(r) ~170,000 glycosylated plasma membrane protein localized to the canalicular surface of hepatocytes in the rat liver. The full-length cDNA of Spgp was isolated from rat, and its expression was characterized in situ and in transfected cells. The expression of Spgp correlates with the differentiation of hepatocytes and is seen only in late liver development. It is not observed in hepatoma cell lines. The physiological function of Spgp in liver is unknown, but it maps to 2q31 in humans, in the vicinity of liver transport disorders for bile acids and cholesterol. Spgp may therefore be involved in some aspect of bile acid or cholesterol metabolism. Spgp transfectants have a low level resistance to Taxol but not to other drugs that form part of the multidrug resistance phenotype. This resistance is reversible by the Pgp-reversing agents cyclosporin A, PSC833, and verapamil, suggesting a conservation in some functions of Pgps across large evolutionary distance.
AB - The sister gene of P-glycoprotein (Spgp) is a liver-specific ATP- binding cassette protein highly related to the P-glycoprotein (Pgp) family (S. Childs et al., Cancer Res., 55: 2029-2034, 1995). Spgp appears to be related to the Pgp family by an ancient duplication occurring before the division of fish and mammals. P-Glycoproteins have diverse functions including broad specificity multidrug resistance in cell lines and tumors, detoxification of tissues such as the intestine and blood-brain barrier, and phosphatidylcholine transport in liver. Spgp is a M(r) ~170,000 glycosylated plasma membrane protein localized to the canalicular surface of hepatocytes in the rat liver. The full-length cDNA of Spgp was isolated from rat, and its expression was characterized in situ and in transfected cells. The expression of Spgp correlates with the differentiation of hepatocytes and is seen only in late liver development. It is not observed in hepatoma cell lines. The physiological function of Spgp in liver is unknown, but it maps to 2q31 in humans, in the vicinity of liver transport disorders for bile acids and cholesterol. Spgp may therefore be involved in some aspect of bile acid or cholesterol metabolism. Spgp transfectants have a low level resistance to Taxol but not to other drugs that form part of the multidrug resistance phenotype. This resistance is reversible by the Pgp-reversing agents cyclosporin A, PSC833, and verapamil, suggesting a conservation in some functions of Pgps across large evolutionary distance.
UR - http://www.scopus.com/inward/record.url?scp=0032530533&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032530533&partnerID=8YFLogxK
M3 - Article
C2 - 9751629
AN - SCOPUS:0032530533
SN - 0008-5472
VL - 58
SP - 4160
EP - 4167
JO - Cancer Research
JF - Cancer Research
IS - 18
ER -