Characterization and detection of cellular and proteomic alterations in stable stathmin-overexpressing; taxol-resistant BT549 *** cancer cells using offgel IEF/PAGE difference gel electrophoresis.
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Characterization and detection of cellular and proteomic alterations in stable stathmin-overexpressing; taxol-resistant BT549 *** cancer cells using offgel IEF/PAGE difference gel electrophoresis.

Mutat Res. 2010 Aug 31;

Authors: Balasubramani M, Nakao C, Uechi GT, Cardamone J, Kamath K, Leslie KL, Balachandran R, Wilson L, Day BW, Jordan MA

Stathmin/oncoprotein 18, a protein that regulates microtubule dynamics, is highly expressed in a number of tumors including leukemia, lymphoma, neuroblastoma, ***, ovarian, and prostate cancers. High stathmin levels have been associated with the development of resistance to the widely-used anticancer drug taxol (((R))Taxol, paclitaxel). The mechanisms of stathmin-mediated taxol resistance are not well-understood at the molecular level. To better understand the role of stathmin in taxol resistance, we stably overexpressed stathmin two-fold in BT549 human *** cancer cells and characterized several cell processes involved in the mechanism of action of taxol. After stable overexpression of stathmin, neither the cell doubling time nor the mitotic index was altered and the microtubule polymer mass was reduced only modestly (by 18%). Unexpectedly, microtubule dynamicity was reduced by 29% after stathmin overexpression, resulting primarily from reduction in the catastrophe frequency. Sensitivity to taxol was reduced significantly (by 44%) in a clonogenic assay, and stathmin appeared to protect the cells from the spindle-damaging effects of taxol. The results suggest that in the stably-stathmin overexpressing clones, compensatory gene expression occurred that resulted in normal rates of cell proliferation and prevented the increase in catastrophe frequency expected in response to stathmin. Stathmin overexpression protected the cells from taxol-induced abnormal mitoses, and thus induced taxol resistance. Using offgel IEF/PAGE difference gel electrophoresis, we identified a number of proteins whose expression is reduced in the taxol-resistant stathmin-overexpressing cell lines, including proteins involved in the cytoskeleton and cell structure, the stress response, protein folding, glycolysis, and catalysis.

PMID: 20816848 [PubMed - as supplied by publisher]

Read the complete post at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=20816848&dopt=Abstract

Posted 8 Sep 2010 12:32 PM by pubmed: neuroblastoma
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