MOLECULAR MECHANISMS OF MULTI-STAGE CARCINOGENESIS

理解分子基础的实验方法 多阶段癌变的重点是解开细胞如何发生的谜团 监管是在多重影响下发生的。因此， 这些结果将是对信号成分研究的独特补充 转导途径在很大程度上是在隔离许多其他方面完成的 细胞调节。这项调查的主要观点是 信号转导酶蛋白激酶C(PKC)，也称为 促进肿瘤的佛波醇酯受体和编码的蛋白质 已证明在细胞内信号中起作用的癌基因 转导，如src、ras、raf、mye和jun。一种分子方法 将用于改造小鼠胚胎C3H信号转导装置 10T1/2细胞，并分析这些细胞表型的影响。自.以来 这项研究的主要主题是由 PKC这项工作的一大部分是为了理解 了解PKC功能和调控的生物化学以及了解更多关于 PKC的分子和细胞生物学。多个因素的相互作用 同时，还将研究细胞信号转导的要素 时间到了。其中一个目标是将这些独立的数据组合在一起，以开发出一个 更好地了解细胞中整合了 转导细胞外信号以产生单一结果。这是有可能的 某些细胞和品系小鼠对促癌剂的抗药性 例如佛波酯涉及综合装置中的改变 使对这种耐药细胞的研究变得有用。最后，体细胞遗传学 将开发一种系统来研究跨细胞质阶段的 始于PKC，终于激活的细胞信号转导 基因转录的结果。后一项研究，连同以下信息 将得到关于相互作用的信号转导，将使 有可能对这一过程有更完整的了解 细胞信号转导及其在多阶段中的作用 致癌。

The experimental approach to understanding the molecular basis of multistage carcinogenesis focuses on unraveling the puzzle of how cellular regulation occurs in the presence of multiple influences. As such the results will uniquely complement studies of components of signal transduction paths done largely in isolation of the many other facets of cellular regulation. The primary points of this investigation are the signal transducing enzyme protein kinase C (PKC), also known to be the receptor for tumor promoting phorbol esters, and proteins encoded by oncogenes that have demonstrated roles in intracellular signal transduction, such as src, ras, raf, mye, and jun. A molecular approach will be used to modify the signal transducing apparatus of mouse embryo C3H 10T1/2 cells and to analyze the effects of these cellular phenotype. Since the major subject of this investigation is signal transduction mediated by PKC a large segment of the effort is to be put into understanding the biochemistry of PKC function and regulation as well as to learn more about the molecular and cellular biology of PKC. The interactions of multiple elements of cellular signal transduction will be investigated at the same time. One of the goals is to combine these separate data to develop a better idea of the molecular apparatus in cells that integrates the transduced extracellular signals to yield a single outcome. It is probable that resistance of some cells and strains of mice to tumor promoting agents such as phorbol esters involves alterations in the integrative apparatus making study of such resistant cells useful. Lastly, somatic cell genetics system will be developed for investigating the transcytoplasmic phase of cellular signal transduction that begins with PKC and ends with activation of gene transcription. The latter study, together with the information that will be obtained about the interactions of signal transduction, will make it possible to obtain a more complete understanding of the process of cellular signal transduction and how it is involved in multistage carcinogenesis.