Journal of Agriculture & Life Sciences

The Cancer Stem Cell Marker GSK3b, a Gene involved in Oxidative Stress, Modulates Chemoresistance in Ovarian Cancer
Noelle Cutter, Julia Fiederlein, Brianna McNulty, Cassandra Greco, Kimberly Doyle

Abstract
The leading cause of death from gynecologic malignancies is epithelial ovarian cancer. These tumors are comprised of a highly heterogeneous population of cells, of which only a small subset of stem-like cells possess the ability to regenerate tumors in vivo. These cancer stem cells (CSCs) represent a significant clinical challenge as they are resistant to conventional cancer therapies and play essential roles in metastasis and tumor relapse. While chemotherapy is the preferred treatment modality, chemoresistance severely limits treatment success. It has been hypothesized that cancer stem cells are at the root of this problem. Their ability to self-renew and proliferate is what causes a large number of ovarian cancers to recur and not respond to normal chemotherapeutic treatments. Recent evidence suggests that deregulation of stem cell pathways is a key factor in the onset and maintenance of chemoresistance. Several key markers such as BMI1, FZD1, GGSK3b, NANOG, TWIST1, and OCT4 (POU5F1) are hypothesized to play a central role in the development and differentiation of multiple cell lineages. Recent studies have demonstrated that these markers is required for the carcinogenesis in several cancer types. The aim of this study was to investigate the significance of CSC expression in chemoresistant and sensitive ovarian cancer cancer cell lines. Through the analysis of gene expression in these cell lines, CSC markers could be identified. CSC mRNA expression was detected by real-time quantitative PCR and by gel electrophoresis of PCR products in sensitive and resistant ovarian cell lines. The objective of such an improved delineation is to develop targeted therapy for selective elimination of cancer stem cells with minimal toxicity to normal stem cells. Our research indicates that there were novel changes in gene expression in the chemoresistant cell lines, specifically involving GSK3b. Further research is needed to gain better understanding of the role that these genes specifically play in cancer survival, metastasis, and chemo resistance.

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