Abstract 2107: Downregulation of ASPP2 in choriocarcinoma contributes to increased migratory potential through Src activation
Cancer Research(2011)
Abstract
Gestational choriocarcinoma is a malignant tumour derived from placental trophoblast and is the most aggressive member of gestational trophoblastic disease (GTD). Apoptotic stimulating protein of p53-2 (ASPP2) is a tumor suppressor member of the ASPP family which transactivates p53-dependent apoptotic pathway. In this study, we examined the expression profile of ASPP2 in choriocarcinoma in comparison with normal placentas and hydatidiform moles which is a type of GTD that carries malignant potential. Results from quantitative PCR and immunohistochemical studies showed that downregulation of ASPP2 was detected in choriocarcinoma at both RNA and protein levels. ASPP2-transfected choriocarcinoma cells (namely JEG-3 and JAR) showed an increase in apoptosis and a decrease in cell migration as detected by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and wound healing assays respectively, illustrating the complex action of ASPP2 on cell functions other than program cell death. Transfection of ASPP2 but not ASPP1, another tumor suppressive member of the ASPP family, decreased Src-pY416 phosphorylation, suggesting an inactivating effect of ASPP2 on Src. Moreover, this ASPP2-induced inactivation of Src could be abolished by RNA interference using Csk small interfering RNA (siRNA). All these findings suggested that the ability of ASPP2 to attenuate Src activation was specific to ASPP2 in a Csk dependent manner. Taken together, we demonstrated a loss of tumor suppressive ASPP2 in choriocarcinoma with effects on cell migration as well as apoptosis. We also unveiled a possible mechanistic link between ASPP2 and Csk/Src signaling pathway, implicating the multiple cellular functions of ASPP2. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2107. doi:10.1158/1538-7445.AM2011-2107
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Key words
choriocarcinoma,aspp2
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