Bleomycin treatment of A549 human lung cancer cells results in association of MGr1-Ag and caveolin-1 in lipid rafts.

Abstract

Bleomycin treatment of A549 cells induces senescence rather than apoptosis, a more usual response of cancer cells to cytotoxic drugs. We have previously shown that upregulation of caveolin-1, the main structural component of caveolae, plays a key role in this process. In order to gain a better understanding of the molecular basis of this phenomenon, caveolin-1-enriched microdomains of untreated and bleomycin-treated growth-arrested A549 cells were analysed for differential protein expression using 2-D DIGE followed by LC-MS/MS. One of these differentially expressed proteins was found to be the multidrug resistance-associated protein (MGr1-Ag). We show that MGr1-Ag becomes partly localised in lipid rafts following bleomycin treatment, and that MGr1-Ag and caveolin-1 occur in a common protein complex in vivo using co-immunoprecipitation studies. GST pull-down assays demonstrated an increased interaction between MGr1-Ag and caveolin-1 following bleomycin treatment in vitro. Our results reveal MGr1-Ag as a novel lipid raft protein; its increased association with caveolin-1 in bleomycin-induced cell cycle arrest and subsequent cellular senescence might contribute to the success of chemotherapy.

• Authors: Annett Linge, Paula Meleady, Michael Henry, Martin Clynes, Michael Kasper, Kathrin Barth
• Journal: The international journal of biochemistry & cell biology (Int J Biochem Cell Biol) Vol. 43 Issue 1 Pg. 98-105 (Jan 2011) ISSN: 1878-5875 [Electronic] Netherlands
• PMID: 20937408 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Elsevier Ltd. All rights reserved.

Chemical References

• Antigens, Neoplasm
• Antineoplastic Agents
• Caveolin 1
• MGr1-antigen, human
• Bleomycin

Topics

• Adenocarcinoma (drug therapy, genetics, metabolism)
• Adenocarcinoma of Lung
• Antigens, Neoplasm (genetics, metabolism)
• Antineoplastic Agents (pharmacology, therapeutic use)
• Apoptosis (drug effects)
• Bleomycin (pharmacology, therapeutic use)
• Caveolae (metabolism)
• Caveolin 1 (genetics, metabolism)
• Cell Cycle (drug effects)
• Cellular Senescence (drug effects)
• Gene Expression (drug effects)
• Humans
• Immunoprecipitation
• Lung Neoplasms (drug therapy, genetics, metabolism)
• Tumor Cells, Cultured