Shen J, Hughes C, Chao C, Cai J, Bartels C, Gessner T, Subjeck J
Proc Natl Acad Sci U S A. 1987 May;84(10):3278-82. doi: 10.1073/pnas.84.10.3278.
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.
哺乳动物细胞中的葡萄糖调节蛋白（GRP）系统由葡萄糖剥夺、缺氧、钙离子载体A23187和2-脱氧葡萄糖诱导产生。在中国仓鼠卵巢细胞中，主要的GRP分子量约为76、97和170 kDa。去除这四种诱导GRP产生的应激因素中的任何一种，都会导致GRP的协同抑制以及70和89 kDa主要热休克蛋白的诱导。施加这四种诱导GRP产生的条件中的任何一种，都会导致对药物阿霉素的抗性显著增加。去除每种诱导GRP产生的条件会导致这种抗性迅速消失，其方式与GRP的抑制相关。GRP诱导的细胞对阿霉素的保留并不能解释诱导的耐药性。当用抗76-kDa GRP的抗体检测RIF体外/体内肿瘤系统时，在从肿瘤中心区域获得的细胞中观察到这种GRP显著增加。由于肿瘤发展过程中可能发生缺氧和/或营养剥夺，肿瘤中的GRP诱导状态可能赋予对阿霉素治疗的抗性。
