HUMAN ENDOGENOUS RETROVIRUSES IN COLON CANCER

目的是研究人类内源性 逆转录病毒在结肠癌发病机制中的作用， 遗传倾向 此外，我们计划调查 逆转录病毒基因产物可能提供早期标记物， 在疾病的初始阶段（发育不良和息肉）进行检测。 Southern印迹杂交将提供关于 内源性逆转录病毒序列在正常结肠粘膜中的整合， 结肠肿瘤 将使用北方印迹分析来检查 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 （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 表征这些的分子结构和功能特性 假定的基因产物，并使用“原位”杂交来验证我们的 生化发现 逆转录病毒基因产物可提供特异性 监测的初始阶段以及进展的标志， 肿瘤性疾病 我们还将测试遗传的概念 结肠癌的易感性，通过扩展我们的分子和生物化学 遗传性结肠息肉病的研究进展 特异性前病毒 单位，表现为垂直传递的孟德尔基因，可能 构成癌症遗传易感性的基质， 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.