PMID- 9144315 OWN - NLM STAT- MEDLINE DCOM- 19970806 LR - 20211203 IS - 0300-8177 (Print) IS - 0300-8177 (Linking) VI - 170 IP - 1-2 DP - 1997 May TI - Differential effect of glucose deprivation on MAPK activation in drug sensitive human breast carcinoma MCF-7 and multidrug resistant MCF-7/ADR cells. PG - 23-30 AB - We have investigated the effect of glucose deprivation treatment on the activation of mitogen activated protein kinases (MAPKs) in the drug-sensitive human breast carcinoma cells (MCF-7) and its drug resistant variant (MCF-7/ADR) cells. Western blots and in-gel kinase assays showed that glucose free medium was a strong stimulus for the activation of MAPK in MCF-7/ADR cells. No activation was seen in MCF-7 cells. MAPK was activated within 3 min of being in glucose free medium and it remained activated for over 1 h in MCF-7/ADR cells. After being returned to complete medium, 1 h was required for the MAPK to become deactivated. To investigate whether alternative sources of ATP could inhibit glucose deprivation induced MAPK activation, we added glutamine and glutamate to glucose deprived medium. The addition of glutamine did not reverse glucose deprivation induced MAPK activation in MCF-7/ADR cells. The addition of glutamate, however, decreased the MAPK activation and the length of time of activation. We observed an increase greater than three fold in MEK, Raf, Ras, and PKC activity with glucose deprivation in MCF-7/ADR cells. This suggests that glucose deprivation-induced MAPK activation is mediated through this signal transduction pathway. FAU - Gupta, A K AU - Gupta AK AD - Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan 48073, USA. FAU - Lee, Y J AU - Lee YJ FAU - Galoforo, S S AU - Galoforo SS FAU - Berns, C M AU - Berns CM FAU - Martinez, A A AU - Martinez AA FAU - Corry, P M AU - Corry PM FAU - Wu, X AU - Wu X FAU - Guan, K L AU - Guan KL LA - eng GR - CA44550/CA/NCI NIH HHS/United States GR - CA48000/CA/NCI NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - Netherlands TA - Mol Cell Biochem JT - Molecular and cellular biochemistry JID - 0364456 RN - 0 (Proto-Oncogene Proteins) RN - 0RH81L854J (Glutamine) RN - 3KX376GY7L (Glutamic Acid) RN - 80168379AG (Doxorubicin) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-raf) RN - EC 2.7.11.13 (Protein Kinase C) RN - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases) RN - EC 2.7.11.25 (MAP Kinase Kinase Kinase 1) RN - EC 2.7.11.25 (MAP3K1 protein, human) RN - EC 3.6.5.2 (ras Proteins) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Breast Neoplasms MH - Calcium-Calmodulin-Dependent Protein Kinases/*metabolism MH - Cell Line MH - Doxorubicin/toxicity MH - *Drug Resistance, Multiple MH - Enzyme Activation/drug effects MH - Female MH - Glucose/*pharmacology MH - Glutamic Acid/pharmacology MH - Glutamine/pharmacology MH - Humans MH - Kinetics MH - *MAP Kinase Kinase Kinase 1 MH - Protein Kinase C/metabolism MH - Protein Serine-Threonine Kinases/metabolism MH - Proto-Oncogene Proteins/metabolism MH - Proto-Oncogene Proteins c-raf MH - Signal Transduction MH - Tumor Cells, Cultured MH - ras Proteins/metabolism EDAT- 1997/05/01 00:00 MHDA- 1997/05/01 00:01 CRDT- 1997/05/01 00:00 PHST- 1997/05/01 00:00 [pubmed] PHST- 1997/05/01 00:01 [medline] PHST- 1997/05/01 00:00 [entrez] AID - 10.1023/a:1006890316102 [doi] PST - ppublish SO - Mol Cell Biochem. 1997 May;170(1-2):23-30. doi: 10.1023/a:1006890316102.