PATHOLOGY IN ANTICANCER/CANCER SUPPRESSOR REGULATION

癌变是一个多步骤的过程，其结果是病理 控制细胞增殖和分化的缺陷和 从获得侵袭性和转移性潜能。同样 重要的是，癌症的发生与癌症的发展有关 对抗这一过程的机制中的异常 致癌。许多研究都支持这一观点。存在与意义 抗癌/抑癌(AC/CS)机制与多种AC/CS 已鉴定的基因包括Rb-1，P53，Wilm‘s抑制基因， 与结肠癌相关的DCC基因，以及拮抗 EJras的转化效应，即Krev-1和RRG。尽管 这些观察的重要性毋庸置疑，这是一个非常重要的问题 抗癌/抑癌基因的表达情况如何 生物和分子调控的活动？的具体目标 这笔拨款是为了回答这些问题。建议的实验是 根据我们最近的发现，聊天时不会改变手机的 增殖潜能、分化及相关过程可诱导 多种类型的AC/CS活动。差异化可以使 诱导产生抗癌作用的未转化细胞 物理/化学制剂和Ejras；差异化可以使 自发地，SV40转化的细胞恢复到未转化的状态 并变得对再转变产生抵抗力。区别也会抑制 转化型SV40大T癌蛋白在CaN治疗中的表达 用二甲基亚砜。调节其中许多的分子机制 调控事件似乎主要涉及转录过程。 事实上，最近的研究结果表明，分化可能影响AC/CS 通过调节交易因子的组成来调节活动 控制SV40和金属硫蛋白II的活性，基因调控 序列。因此，我们这次拨款的目标是进行更多的调查 正是诱导这些活动的生物学基础，并 确定并描述调节 AC/CS活性的表达。这些研究应该提供重要的 关于致癌的病理学和新方法的信息 用于癌症治疗和预防。

Carcinogenesis is a multistep process that results from pathological defects in the control of cellular proliferation and differentiation and from the acquisition of invasive and metastatic potentialities. Equally important, carcinogenesis is associated with the development of abnormalities in mechanisms that antagonize the process of carcinogenesis. Numerous studies support the. existence and significance of anticancer/cancer suppressor (AC/CS) mechanisms and multiple AC/CS genes have been identified including Rb-1, p53, Wilm's suppressor gene, the DCC gene associated with colon cancer, and genes that antagonize the transforming effect of EJras, i.e. Krev-1 and rrg. Despite the unequivocal importance of these observations, a very important question remains unanswered.How is the expression of anticancer/cancer suppressor activity biologically and molecularly regulated? The specific aims of this grant are to answer these questions. The proposed experiments are based on our recent discoveries Chat without changing a cell's proliferative potential, differentiation and related processes can induce multiple types of AC/CS activity. Differentiation can make nontransformed cells resistant to carcinogenesis induced by physical/chemical agents and EJras; differentiation can make spontaneously and SV40 transformed cells revert to a nontransformed state and become resistant to retransformation.Differentiation can also repress expression of the transforming SV40 large T oncoprotein as can treatment with DMSO. The molecular mechanisms that mediate many of these regulatory events appear to primarily involve transcriptional processes. Recent results in fact suggest that differentiation may effect AC/CS activity by modulating the composition of transacting factors that control the activity of SV40 and metallothionein II, genetic regulatory sequences. Our goals in this grant are therefore to investigate more precisely the biological basis for induction of these activities and to identify and characterize the transacting factors that regulate the expression of AC/CS activity. These studies should provide important information concerning the pathology of carcinogenesis and new approaches for cancer therapy and prevention.