Coinduction of glucose-regulated proteins and doxorubicin resistance in Chinese hamster cells.
The glucose-regulated protein (GRP) system in mammalian cells is induced by glucose deprivation, anoxia, the calcium ionophore A23187, and 2-deoxyglucose. In Chinese hamster ovary cells the major GRPs are approximately equal to 76, 97, and 170 kDa. Removal of each of these four GRP-inducing stresses leads to the coordinate repression of GRPs and induction of the major heat shock proteins at 70 and 89 kDa. The application of each of these four GRP-inducing conditions leads to a significant induction of resistance to the drug doxorubicin. Removal of each GRP-inducing condition results in the rapid disappearance of this resistance in a manner that correlates with the repression of the GRPs. The retention of doxorubicin by GRP-induced cells does not explain the induced drug resistance. When the RIF in vitro/in vivo tumor system is probed with an antibody against the 76-kDa GRP, a significant increase in this GRP is observed in cells obtained from the central regions of tumors. Since hypoxia and/or nutrient deprivation can occur during tumor development, a GRP-induced state in the tumor may confer resistance to doxorubicin treatment.
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D003847:Deoxyglucose / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology*; D004351:Drug Resistance; D005947:Glucose / Q000494:pharmacology; D018840:HSP70 Heat-Shock Proteins; D007700:Kinetics; D008565:Membrane Proteins / Q000096:biosynthesis*
D018840:HSP70 Heat-Shock Proteins; D008565:Membrane Proteins; C018551:glucose-regulated proteins; D000001:Calcimycin; D004317:Doxorubicin; D003847:Deoxyglucose; D005947:Glucose