EXPRESSION OF ONCOGENE PROTEINS IN COLORECTAL TUMORS

细胞原癌基因的激活或突变可能是重要事件 在肿瘤的启动、促进和/或进展中起作用。会议的主要目标是 这项提案中提出的研究是为了评估癌基因的表达 产物，特别是人结肠新鲜组织中的c-ras和c-myc 息肉、原发结肠肿瘤以及这些肿瘤的转移性病变 确定这些原癌基因的异常表达是否与 肿瘤发展的任何阶段。活化的c-ras基因的表达 原癌基因(通过转染法检测)已被证实。 在各种肿瘤中。Myc家族的原癌基因是 在许多恶性肿瘤中放大，有时在特定的阶段和指示性的 对预后的影响。在一些肿瘤细胞中，c-myc和c-ras都是原癌基因 都是异常表达的。随着新鲜人类肿瘤的出现 M.D.安德森医院和肿瘤研究所的组织，假设 这些癌基因中的一个或两个的异常表达与某些 将对结肠恶性肿瘤的各个阶段进行检测。结肠肿瘤是一种 由于家族性息肉病，这些研究的系统特别好 结肠(FPC)综合征，从息肉到癌症进展缓慢 除非进行手术干预，否则这是不可避免的。因此，我们将分析 可以获得的息肉类型，包括来自FPC患者的息肉，以及 Dukes‘s各期(原位、B1、 B2、C、D和不同器官的转移)。这项研究的重点是 这些癌基因的蛋白质产物，包括确定患病率 突变的c-ras蛋白，以及固定组织上的免疫过氧化物酶研究 标本来检查肿瘤内的单个细胞，将它们与 邻近的正常组织。后者的研究将在#年进行。 与本组织病理学系的一名成员合作 机构。因此，这项研究将是第一次全面 评估新鲜豪曼组织中的原癌基因产物。还包括 在这项研究中，正在与研究所的成员合作努力 肿瘤细胞的细胞遗传学及其mRNA和蛋白的表达 癌基因结构。所获得的数据应有助于理解 C-ras基因异常表达可能的机制(S) 参与肿瘤的发生。

Activation or mutation of cellular proto-oncogenes may be important events in tumor initiation, promotion and/or progression. The main goals of the studies presented in this proposal are to assess the expression of oncogene products, in particular, c-ras and c-myc in fresh tissue from human colon polyps, primary colon tumors and in metastatic lesions of these tumors, to determine if abnormal expression of these proto-oncogenes correlates with any of the stages of tumor development. The expression of activated c-ras proto-oncogenes (as determined by transfection assays) has been implicated in a variety of tumors. The proto-oncogenes of the myc family are amplified in many malignancies, sometimes at specific stages and indicative of prognosis. In some tumor cells, both a c-myc and c-ras proto-oncogene are aberrantly expressed. With the availability of fresh human tumor tissues at M.D. Anderson Hospital and Tumor Institute, the hypothesis that aberrant expression of one or both of these oncogenes correlates with some of the stages of colon malignancies will be tested. Colon tumors are a particularly good system for these studies because of familial polyposis coli (FPC) syndromes, in which slow development from polyp to carcinoma is inevitable barring surgical intervention. Thus, we will analyze as many types of polyps as can be obtained, including polyps from FPC patients, and malignant colorectal carcinomas of each of the Dukes' stages (in situ, B1, B2, C, D, and metastases to different organs). This study focuses on the protein products of these oncogenes, including determining the prevalence of mutated c-ras proteins, and immunoperoxidase studies onfixed tissue specimens to examine individual cells within the tumor, comparing them to adjacent normal tissues. The latter studies will be performed in collaboration with a member of the Pathology Department of this Institution. Thus, this study will represent the first to comprehensively assess the proto-oncogene products in fresh hauman tissue. Also included in this study are collaborating efforts with members of the Institution on the cytogenetics of the tumor cells as well as expression of mRNA and oncogene structure. The data obtained should be useful in understanding the mechanism(s) by which aberrant expression of c-ras genes may participate in tumorigenesis.