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Putative Role for the GTPase, hGBP-1, in Tumor Cell Proliferation and Resistance to Paclitaxel

Chowdhury, Shilpi
http://rave.ohiolink.edu/etdc/view?acc_num=toledo1404233181

Abstract Details

2014, Master of Science, University of Toledo, Biology (Cell-Molecular Biology).
Cell proliferation and cell death are essential, yet opposing, cellular processes that maintain homeostasis. Disruption of these programmed cellular processes may lead to cancer progression, often accompanied by resistance to chemotherapy. During cancer progression, interferons production can lead to the induction of human Guanylate-Binding Protein-1 (hGBP-1). hGBP-1 retards the proliferation of endothelial cells but its role in carcinomas is not fully understood. The present study demonstrates that ectopic expression of hGBP-1 inhibits the proliferation of MCF-7 breast cancer and 2fTGH sarcoma cells, but its expression in DU145 prostate cancer cells does not influence their proliferation. In contrast, IFN-γ or IFN-2αA treatment does not influence the proliferation of MCF-7 and 2fTGH cells, but the proliferation of DU145 cells is inhibited by IFN-α2a treatment. This indicates that interferons do not universally inhibit the proliferation of carcinomas. Some breast and ovarian cancer cell lines show elevated expression of hGBP-1 when they are made resistant to paclitaxel. The ectopic expression of hGBP-1 in OVCAR8 cells protects the cells from paclitaxel-induced cytotoxicity. This protection by hGBP-1 is also provided in MCF-7 breast cancer and SKOV-3 ovarian cancer cells, through inhibition of paclitaxel-induced apoptosis. The expression of hGBP-1 is not always elevated in paclitaxel-resistant MCF-7 breast and A2780 ovarian cancer cell lines suggesting that up-regulation of hGBP-1 is not the only mechanism for the development of resistance to paclitaxel. Analysis of the levels of hGBP-1 mRNA in primary and recurrent ovarian tumors demonstrates that up-regulation of the expression of hGBP-1 is associated with the development of paclitaxel or docetaxel resistance in ovarian cancer patients. Elevated expression of TUBB3, a β-tubulin isotype, can also be involved in paclitaxel-resistance in carcinoma cells. In ovarian tumors, the level of TUBB3 mRNA is elevated prior to chemotherapy, suggesting that elevated expression of TUBB3 may be associated with intrinsic resistance to paclitaxel treatment. Moreover, the expression of TUBB3 is not strictly associated with the expression of hGBP-1 in primary and recurrent tumors. Together, these results suggest that hGBP-1 may be a diagnostic marker for the development of resistance to taxane treatment in ovarian tumors.
Deborah Vestal, Ph.D (Committee Chair)
127 p.
Biology; Cellular Biology; Molecular Biology
Guanylate-Binding proteins, Beta-tubulin, Paclitaxel, Tumor

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Citations

  • Chowdhury, S. (2014). Putative Role for the GTPase, hGBP-1, in Tumor Cell Proliferation and Resistance to Paclitaxel [Master's thesis, University of Toledo]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1404233181

    APA Style (7th edition)

  • Chowdhury, Shilpi. Putative Role for the GTPase, hGBP-1, in Tumor Cell Proliferation and Resistance to Paclitaxel. 2014. University of Toledo, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=toledo1404233181.

    MLA Style (8th edition)

  • Chowdhury, Shilpi. "Putative Role for the GTPase, hGBP-1, in Tumor Cell Proliferation and Resistance to Paclitaxel." Master's thesis, University of Toledo, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1404233181

    Chicago Manual of Style (17th edition)

toledo1404233181
361
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This open access ETD is published by University of Toledo and OhioLINK.