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Identification of Thioredoxin-Interacting Protein as a Potential Mediator of Anoikis-Resistance in Ovarian Cancer

Spaeth-Cook, Douglas M, Jr
http://rave.ohiolink.edu/etdc/view?acc_num=osu1494314758133333

Abstract Details

2017, Master of Science, Ohio State University, Public Health.
Epithelial ovarian cancer (EOC) is most commonly diagnosed at advanced stages, resulting in poor prognoses. Unlike most cancers, EOC does not typically spread hematogenously or lymphatically, opting instead for passive diffusion into the peritoneal cavity. This paper proposes a model that simulates the transition from primary tumor to disseminated disease using adherent and non-adherent cell culture conditions. Temporal transcriptomic analysis was performed on a well-studied ovarian cancer cell line that was subjected to this model. This resulted in the identification of TXNIP as a primary gene of interest. To validate the significance of this gene, a TXNIP knockdown cell line was developed using shRNA. Spheroid formation of the knockdown cell line in vitro was analyzed qualitatively and quantitatively using live-cell imaging. The knockdown was found to exhibit an anoikis-resistant phenotype. To assess prognostic relevance of the gene, the TCGA ovarian cancer dataset was queried for differences in patient survival outcomes based on categorization of high or low TXNIP expression in tumor samples, relative to median expression, at the time of initial surgery. High TXNIP expression was found to correlate significantly with longer overall and progression free survival in early stage patients. The same was not true for late stage patients. To assess the effect of platinum agents on TXNIP, carboplatin was used to treat three ovarian cancer cell lines grown in non-adherent conditions for 48 hours. Western blots confirmed that 100 nM carboplatin did not affect TXNIP expression at 48 hours. The findings of this paper lead us to believe that TXNIP is a potential mediator of anoikis-resistance in ovarian cancer.
Courtney Hebert, MD, MS (Advisor)
Randi Foraker, PhD (Committee Member)
James Chen, MD (Committee Member)
60 p.
Bioinformatics; Oncology; Public Health
Ovarian cancer; anoikis; live cell imaging; peritoneal cancer; TXNIP; Thioredoxin-Interacting Protein

Recommended Citations

Citations

  • Spaeth-Cook, Jr, D. M. (2017). Identification of Thioredoxin-Interacting Protein as a Potential Mediator of Anoikis-Resistance in Ovarian Cancer [Master's thesis, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1494314758133333

    APA Style (7th edition)

  • Spaeth-Cook, Jr, Douglas. Identification of Thioredoxin-Interacting Protein as a Potential Mediator of Anoikis-Resistance in Ovarian Cancer. 2017. Ohio State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1494314758133333.

    MLA Style (8th edition)

  • Spaeth-Cook, Jr, Douglas. "Identification of Thioredoxin-Interacting Protein as a Potential Mediator of Anoikis-Resistance in Ovarian Cancer." Master's thesis, Ohio State University, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=osu1494314758133333

    Chicago Manual of Style (17th edition)

osu1494314758133333
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© 2017, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.