Stimulation of dopamine D2S receptor introduced in Balb/c-3T3 cells induces Galphai3-dependent transformation. Galphai3 interacts with DED2-containing protein, TNFAIP8, in yeast mating and in FLAG-TNFAIP8 transfected Balb/c-3T3 cells. TNFAIP8 inhibits caspase-8 activity and is elevated in certain cancers as well as in metastatic, radiation resistant, chemo-resistant and angiogenic tumours. This study looks at Galphai3 activation of TNFAIP8 leading to the inhibition of TNFalpha-induced cell death in Balb/c-3T3 cells coexpressing D2S and either TNFAIP8 over-expression or TNFAIP8 antisense-knockdown with assays for foci formation, cell death and executioner caspase activation. The data showed D2S increases basal foci formation; this is blocked in TNFAIP8 antisense cells. D2S activation further increases foci formation; also completely blocked in TNFAIP8 antisense cells. D2S activation reduces cell death except in TNFAIP8 antisense cells. D2S activation reduces caspase-active cells. These results show that D2S mediated inhibition of caspase activity and death resulting in transformation is dependent on TNFAIP8.
| Identifer | oai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/28128 |
| Date | January 2009 |
| Creators | Laliberte, Ben |
| Publisher | University of Ottawa (Canada) |
| Source Sets | Université d’Ottawa |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | 106 p. |
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