Abstract 274: Cited2, a novel EGFR-induced coactivator, plays a key role in lung cancer progression

Abstract

Abstract Aberrant expression and function of epidermal growth factor receptor (EGFR) are reported in most lung cancer cases and are correlated with poor prognosis. However, the role of many downstream effectors associated with abnormal EGFR signaling is not clear in cancer progression. Cited2, a novel transcriptional co-activator was identified to be induced by hyperactive EGFR mutant L858R in lung cancer cells. Overexpression of Cited2 in CL1-0 lung cancer cells allowed cell to survive in serum free condition. Knockdown of Cited2 attenuated cell growth, leading to G1/S cell cycle arrest. Through microarray analysis, we identified that expression of E2F3 and its downstream gene targets were blocked in Cited2-silenced cells. Overexpression of Cited2 enhanced E2F3 expression, supporting that Cited2 regulates E2F3 expression. By chromatin immunoprecipitation assay, we found Cited2 bound to E2F3 promoter. In addition to affecting cell growth, knockdown of Cited2 promoted cell senescence with flat and enlarged cell morphology, and increased senescence-associated ß-galactosidase activity. Through western blot analysis, we found Cited2-silencing induced p53 and p21 expression. Overexpression of Cited2 further enhanced tumor growth in nude mice. Clinical analysis showed that Cited2 was highly expressed in lung cancer but not in normal tissues. These data demonstrate that Cited2 plays a key role in lung cancer progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 274.