HUMAN ENDOGENOUS RETROVIRUSES IN COLON CANCER

其目的是研究人类内源性的可能作用。 逆转录病毒在结肠癌发病机制中的作用 遗传易感性。此外，我们计划调查 逆转录病毒基因产物可能提供早期标志物 在疾病的初始阶段(发育不良和息肉)进行检测。 Southern印迹杂交将提供有关模式的信息 内源性逆转录病毒序列在正常结肠粘膜和正常结肠组织中的整合 结肠肿瘤。Northern印迹分析将用于检查 这些序列的转录，其表达模式可以是 与肿瘤疾病的特定方面或阶段相关的 (可能包括从息肉或发育不良进展到 腺癌)。利用cdna克隆和杂交瘤技术，我们计划 描述这些化合物的分子结构和功能特性 并使用“原位”杂交来验证我们的 生化结果。逆转录病毒基因产品可能提供特异的 用于监测初始阶段以及进展情况的标记 肿瘤疾病。我们还将测试基因的概念 通过扩大我们的分子和生物化学易患结肠癌 遗传性结肠息肉病的研究进展。特异性前病毒 表现为垂直传播的孟德尔基因的单位，可能 构成癌症遗传易感性的底物及其 表达可能与某些临床或病理方面相关。 结肠肿瘤。

The aim is to investigate the possible role of human endogenous retroviruses in the pathogenesis of colon cancer and possibly in its genetic predisposition. In addition, we plan to investigate the possibility that retroviral gene products may provide early markers for the detection of the disease at its initial stages (dysplasia and polyps). Southern blot hybridization will provide information on the pattern of integration of endogenous retroviral sequences in normal colon mucosa and colon tumors. Northern blot analyses will be used to examine the transcription of these sequences, whose pattern of expression can be correlated with particular aspects or stages of the neoplastic disease (possibly including the progression from polyps or dysplasia to adenocarcinoma). Using cDNA cloning and hybridoma technology, we plan to characterize the molecular structure and functional properties of these putative gene products and to use "in situ" hybridization to validate our biochemical findings. Retroviral gene products may provide specific markers to monitor the initial stages as well as the progression of the neoplastic disease. We will also test the concept of genetic predisposition to colonic cancer by extending our molecular and biochmical approach to the study of hereditary polyposis of colon. Specific proviral units, which behave as vertically transmitted mendelian genes, may constitute the substrate for genetic predisposition to cancer and their expression may correlate with certain clinical or pathologic aspects of colonic neoplasia.