Abstract 4819: Wolf-Hirschhorn syndrome candidate 1, a histone lysine methyltransferase, is involved in human carcinogenesis

Abstract

Abstract A number of histone methyltransferases have been identified and biochemically characterized, but the pathological roles of their dysfunction in human diseases like cancer are not well understood. Here, we demonstrate that Wolf-Hirschhorn syndrome candidate 1 (WHSC1) plays an important role in human carcinogenesis. Transcriptional levels of this gene are significantly elevated in various types of cancer including bladder and lung cancers. Immunohistochemical analysis using a number of clinical tissues confirmed significant up-regulation of WHSC1 expression in bladder and lung cancer cells at the protein level. Treatment of cancer cell lines with small interfering RNAs targeting WHSC1 significantly knocked down its expression and resulted in the suppression of proliferation. Moreover, knockdown of WHSC1 decreased the cell population of cancer cells at S phase and increased that at G2/M phase through the regulation of genes involved in the Wnt signaling pathway. Furthermore, we found WHSC1 to be interacted with some proteins related to the Wnt pathway including β-catenin. As expression levels of WHSC1 are significantly low in normal tissues, it may be feasible to develop the inhibitors targeting these enzymes as anti-tumor agents which have a minimal risk of adverse reaction. 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 4819. doi:10.1158/1538-7445.AM2011-4819