Characterization of the GBP1 gene associated with the multidrug resistant phenotype in vitroConference Paper
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abstract
Proc Amer Assoc Cancer Res, Volume 45, 2004 597 cDNA array technology comparing transcript expression in paclitaxel resistant breast and ovarian cancer cell lines and to their drug nave parental lines has identified that overexpression of the large GTPase GBP1 (Guanylate Binding Protein 1), is associated with the multidrug resistant phenotype. Northern analysis demonstrates that GBP1 is overexpressed in a large collection of paclitaxel and doxorubicin resistant cell lines. In addition, GBP1 is also overexpressed in the gemcitabine resistant subclone of the ovarian cancer cell line OVCAR5 which does not overexpress MDR1. Analysis of the Cancer Profiling Array (Clontech), which contains cDNA samples from individual normal tissues and matched tumors, demonstrates that GBP1 is broadly expressed in various tissues and their corresponding tumors. The Cancer Cell Line Profiling Array (Clontech), which contains cDNA samples generated from 26 human cancer cell lines treated with 26 different chemical agents, demonstrates that GBP1 is overexpressed 0.5 to 22.2 fold (average 6.8 fold) after 48 hours of paclitaxel exposure and 0.5 to 7.9 fold (average 2.8 fold) after doxorubicin exposure in various cell lines. Finally, forced overexpression of GBP-1 in the human ovarian cancer cell line OVCAR8 leads to a four-fold increase in paclitaxel resistance. These results suggest a role for GBP1 in the development of multidrug resistant phenotype. The extent of the involvement of GBP1 in clinical drug resistance awaits further investigation.
