C-terminal Binding Protein (CtBP) is a transcriptional co-repressor that plays an important role in mammalian development and tumorigenesis. CtBP is known to interact with Ikaros, an important transcriptional regulator in the pituitary; however CtBP itself has not been examined in this gland. I examined the role of CtBP in pituitary cell growth and survival. Compared to control pituitary GH4 cells, CtBP1-deficient cells exhibit reduced proliferation and de-regulation of genes involved in cell cycle and growth factor signaling. CtBP1-deficient cells were more susceptible to hypoxia-induced apoptosis and showed a reduction in hypoxia-induced Ikaros expression. Interactions between CtBP and Ikaros isoforms were demonstrated in pituitary tumor
cell lines. CtBP and Ikaros also bound a common region of the previously characterized Ikaros target, the LDL-R promoter. These results identify oncogenic properties of CtBP1 in the pituitary and set the groundwork for future studies into regulatory roles of CtBP and Ikaros in the
pituitary.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/25555 |
| Date | 31 December 2010 |
| Creators | Dorman, Kathryn |
| Contributors | Asa, Sylvia, Ezzat, Shereen |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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