INDUCTION OF A HUMAN CARBONYL REDUCTASE GENE LOCATED ON CHROMOSOME-21

被引:51
作者
FORREST, GL
AKMAN, S
KRUTZIK, S
PAXTON, RJ
SPARKES, RS
DOROSHOW, J
FELSTED, RL
GLOVER, CJ
MOHANDAS, T
BACHUR, NR
机构
[1] CITY HOPE NATL MED CTR,BECKMAN RES INT,DIV IMMUNOL,DUARTE,CA 91010
[2] CITY HOPE NATL MED CTR,DEPT MED ONCOL & THERAPEUT RES,DUARTE,CA 91010
[3] DIS DETECT INT,IRVINE,CA
[4] UNIV CALIF LOS ANGELES,MED CTR,DEPT MED,LOS ANGELES,CA 90024
[5] NCI,BIOL CHEM LAB,BETHESDA,MD 20205
[6] UNIV CALIF LOS ANGELES,LOS ANGELES CTY HARBOR MED CTR,DEPT PEDIAT,TORRANCE,CA 90509
[7] UNIV MARYLAND,CTR CANC,BALTIMORE,MD 21201
关键词
cDNA; Daunorubicin reductase; Drug metabolism; MCF-7;
D O I
10.1016/0167-4781(90)90050-C
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Carbonyl reductase (EC 1.1.1.184) belongs to the group of enzymes called aldo-keto reductases. It is a NADPH-dependent cytosolic protein with specificity for many carbonyl compounds including the antitumor anthracycline antibiotics, daunorubicin and doxorubicin. Human carbonyl reductase was cloned from a breast cancer cell line (MCF-7). The cDNA clone contained 1219 base paires with an open reading frame corresponding to 277 amino acids encoding a protein of Mr 30375. Southern analysis of genomic DNA digested with several restriction enzymes and analyzed by hybridization with a labeled cDNA probe indicated that carbonyl reductase is probably coded by a single gene and does not belong to a family of structurally similar enzymes. Southern analysis of 17 mouse / human somatic cell hybrids showed that carbonyl reductase is located on chromosome 21. Carbonyl reductase mRNA could be induced 3-4-fold in 24 h with 10 μM 2,(3)-t-butyl-4-hydroxyanisole (BHA), β-naphthoflavone or Sudan 1. © 1990.
引用
收藏
页码:149 / 155
页数:7
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