Tumor gene expression in vitro and in vivo

点击翻译按钮获取中文摘要

Our growth regulation research has been concerned with oncogenes and tumor suppressor genes as positive and negative regulators of normal and neoplastic growth. We have studied the Ras-specific guanine nucleotide exchange factors (Ras-GNEFs), which play a key role in signal transduction, and in activation of the ras proto-oncogene. Most recently, we have begun to investigate E-cadherin, a key cell surface adhesion protein that is a tumor suppressor that is frequently silenced in many epithelial cancers and melanoma. We have found that E-cadherin specifically inhibits the activation of a variety of receptor tyrosine kinases (RTKs) by their physiologic ligands. The inhibition probably results from the formation of a complex between E-cadherin and the RTKs, which restricts the ability of the ligands to bind their cognate RTK with high affinity. This inhibitory activity of E-cadherin is abrogated when it is silenced in tumors, permitting more robust responses to RTKs by their ligands, a widespread phenomemon implicated in the pathogenesis of many tumors. Future studies will examine other mechanisms by which E-cadherin regulates cell growth and the possibility of using E-cadherin as a potential cancer treatment target.