Mitogen-activated protein kinase signaling in drug-resistant neuroblastoma cells.

Abstract

Widespread inherent or acquired resistance to cytotoxic drugs is a major limitation to chemotherapy. There are many mechanisms that contribute to such resistance. In neuroblastomas there is evidence that acquired drug resistance may be associated with altered response to growth factor signals. The ubiquitous mitogen-activated protein kinase (MAPk) cascade, which transmits growth factor signals from the cell membrane to the nucleus, provides a principal mechanism for regulation of cell cycle progression and proliferation. We have shown that there is a relationship between acquired drug resistance in human neuroblastoma cells to doxorubicin, a topoisomerase-2 inhibitor, and to MDL-28842, an inhibitor of S-adenosylhomocysteine hydrolase, and reductions in the activation and nuclear translocation of MAPk.

• Authors: Raymond R Mattingly
• Journal: Methods in molecular biology (Clifton, N.J.) (Methods Mol Biol) Vol. 218 Pg. 71-83 ( 2003) ISSN: 1064-3745 [Print] United States
• PMID: 12616713 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antineoplastic Agents
• 4',5'-didehydro-5'-deoxy-5'-fluoroadenosine
• Doxorubicin
• Adenosine

Topics

• Adenosine (analogs & derivatives, pharmacology)
• Antineoplastic Agents (pharmacology)
• Doxorubicin (pharmacology)
• Drug Resistance, Neoplasm
• Humans
• MAP Kinase Signaling System
• Neuroblastoma
• Phosphorylation
• Tumor Cells, Cultured (drug effects, metabolism)