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A Systems Biology Approach to Validate Potential Targets for the Personalized Therapy of BRCA1 Associated Cancers
Başlık:
A Systems Biology Approach to Validate Potential Targets for the Personalized Therapy of BRCA1 Associated Cancers
Yazar:
Fisher, Timothy B., author.
ISBN:
9780355977011
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (125 pages)
Genel Not:
Source: Masters Abstracts International, Volume: 57-06M(E).
Includes supplementary digital materials.
Advisors: Veena N. Rao Committee members: Michael Powell; E. Shyam P. Reddy.
Özet:
Background and Significance: Epithelial ovarian cancer (EOC) is the leading cause of cancer death from gynecological cancers (1). BRCA1 mutation carriers are at a high risk for developing high-grade-serous ovarian cancer (HGSOC). Our lab has previously shown BRCA1 isoforms to function as tumor suppressors in ovarian cancers. Our group has found wildtype BRCA1, but not the pathogenic mutant BRCA1 protein found in ovarian cancers to bind a sole SUMO conjugating enzyme UBE2I (Ubc9), which promotes proliferation, migration and metastasis of multiple epithelial malignancies including ovarian cancers. We have found UBE2I to be overexpressed in patient-derived BRCA1-mutant (2594delC) HGSOC cells and ovarian tumor samples. Knockdown of UBE2I in vitro resulted in decreased migration and anchorage-independent growth of HGSOC and TNBC cells. Hypothesis: We hypothesize high expression of UBE2I in BRCA1 mutant HGSOC will correlate with the increased expression of Ubc9. If true, it will result in identification of a druggable target for mechanism based targeted therapy for HGSOC. Results: Our initial expression analysis did not depict a great fold change for UBE2I RNA expression and it could be possible that this gene could have a high turnover rate and that is why the fold change is not significant but yet we see protein expression via western blot and IHC analysis. We performed a systems biology pathway analysis and found distinct differences between networks that are active in wild type BRCA1 and mutated BRCA1 HGSOC samples, largely defined by the direct and indirect relationship between the top networks. The observed regulatory changes between samples suggest potential downstream druggable targets that may help in the treatment of BRCA1 mutant HGSOC.
Notlar:
School code: 1943
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(692164.1) | 692164-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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