Tumor gene expression in vitro and in vivo

我们的生长调控研究一直关注癌基因和肿瘤抑制基因作为正常和肿瘤生长的正调控因子和负调控因子。我们研究了ras特异性鸟嘌呤核苷酸交换因子（ras - gnefs），它在信号转导和ras原癌基因的激活中起关键作用。最近，我们开始研究e -钙粘蛋白，这是一种关键的细胞表面粘附蛋白，是一种肿瘤抑制因子，在许多上皮癌和黑色素瘤中经常沉默。我们发现e -钙粘蛋白特异性地抑制多种受体酪氨酸激酶（rtk）的生理配体的激活。这种抑制可能是由于E-cadherin和RTK之间形成了一个复合物，这限制了配体与同源RTK高亲和力结合的能力。当E-cadherin在肿瘤中沉默时，其抑制活性被取消，允许其配体对rtk产生更强的反应，这是一种与许多肿瘤发病机制有关的普遍现象。未来的研究将研究E-cadherin调节细胞生长的其他机制，以及E-cadherin作为潜在癌症治疗靶点的可能性。

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.