The Role of CtBP in Pituitary Tumorigenesis
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 exam...
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Language: | en_ca |
Published: |
2010
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Online Access: | http://hdl.handle.net/1807/25555 |
Summary: | 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. |
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