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PMID: 3106964 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Coinduction of glucose-regulated proteins and doxorubicin resistance in Chinese hamster cells.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 84 ·No. 10 ·1987-05-00 ·Pages 3278-82

Shen J, Hughes C, Chao C, Cai J, Bartels C, Gessner T, Subjeck J

Abstract

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.

MeSH Terms
Animals Calcimycin/pharmacology Cell Line Cricetinae Cricetulus Deoxyglucose/pharmacology Doxorubicin/pharmacology Drug Resistance Glucose/pharmacology HSP70 Heat-Shock Proteins Kinetics Membrane Proteins/biosynthesis
Chemicals
HSP70 Heat-Shock Proteins Membrane Proteins glucose-regulated proteins Calcimycin Doxorubicin Deoxyglucose Glucose
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Shen J
Hughes C
Chao C
Cai J
Bartels C
Gessner T
Subjeck J
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.84.10.3278
Published
1987-05-00
Pages
3278-82
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC304852
Subset
IM
Grants
PHS HHS · 40330-02 · United States
External Links
PubMed source DOI: 10.1073/pnas.84.10.3278 PMC Full Text View journal details
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