Abstract 713: Active hedgehog pathway in human primary gastric tumor models

Abstract

Abstract The hedgehog (Hh) signaling pathway is known to be essential for multiple aspects of embryonic development, and activation of the Hh pathway leads to the development of several human malignancies such as basal cell carcinoma and medulloblastoma. Recent data have implicated a much broader role of the Hh pathway in other human cancer as well as the maintenance of cancer stem cells. Loss-function mutation of Ptc and gain of gunction mutation of Smo in human malignancies make the components in Hh pathway attractive therapeutic targets. However, this pathway is readily deactivated once human tumor cells are propagated in cell culture, a prerequisite of most preclinical human cancer models. In order to identify useful models for the evaluation of novel therapeutics targeting the Hh pathway, we profiled the expression of Ptc, Smo, Gli in a cohort of twenty established human primary gastric tumor models by TaqMan real-time quantitative PCR reaction and immunohistochemistry (IHC). Seven of the twenty models displayed high expression of either Gli-1 or Gli-2. Eight models were found to have high expression level of Shh. And three models were found to have high level of Ptc. The Gli protein expression level is also examined with IHC. High levels of Gli and Shh in the selected models will be very useful to evaluate anticancer drugs against Hh signaling pathway for their drug activity and pharmacodynamic responses. These models, together with the associated clinical and pathological information, provide a unique platform to evaluate the in vivo activities of pharmaceutical agents targeting the Hh pathway. 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 713.