ONCOGENE EXPRESSION IN HUMAN CARCINOMAS

人类癌症中癌基因的表达

• 批准号: 3963061
• 负责人: P H HAND
• 金额: --
• 依托单位: DIVISION OF CANCER BIOLOGY AND DIAGNOSIS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3963061
• 关键词: antigens; breast neoplasms; colon disorder; fibroma; gastrointestinal epithelium; gene expression; genetic manipulation; immunochemistry; immunoperoxidase; inflammation; mammary disorder; monoclonal antibody; neoplasm /cancer genetics; oncogenes; radioimmunoassay

Monoclonal antibodies (MAbs) of predefined specificity have been generated by utilizing a synthetic peptide reflecting amino acid positions 10-17 of the Hu-rasT24 gene product as immunogen. When paraffin-embedded Formalin-fixed tissue sections and the avidin-biotin complex immunoperoxidase methods were used, the RAP (RA, ras; P, peptide) MAbs clearly defined enhanced ras p21 expression in the majority of human colon and mammary carcinomas. Invasive mammary carcinomas demonstrated enhanced ras p21 expression with generally decreasing expression in carcinoma in situ, atypical hyperplasia, and non-atypical hyperplasia. The majority of all abnormal ducts and lobules from fibroadenoma and fibrocystic disease patients were negative, as well as normal mammary and colonic epithelia examined. We have also used the RAP MAbs to define ras p21 protein expression in a spectrum of colonic disease states. Immunohistochemical analyses of individual cells within tissue sections reveal differences in ras p21 expression in colon carcinomas compared with normal colonic epithelium, benign colon tumors and inflammatory or dysplastic-colon lesions. Our data suggest that ras p21 expression is correlated with depth of carcinoma within the bowel wall, and is probably a relatively late event in colon carcinogenesis. Enhanced ras p21 expression was also observed in high grade prostate and bladder carcinomas. We have recently developed quantitative liquid competition RIAs for ras p21 using MAb Y13-259. By the use of a standard of pure recombinant ras p21, we are now able to detect p21 at fM levels, and to determine the number of molecules of p21 per cell. The concomitant use of quantitative RIAs and immunohistochemical analyses of normal, dysplastic and inflammatory disease states, as well as carcinomas, should lead to a better understanding of the role of the ras gene in the genesis of these lesions.

已经产生了预定义的特异性的单抗 通过利用反映10-17位氨基酸的合成肽 HU-rasT24基因产物作为免疫原。石蜡包埋时 福尔马林固定的组织切片和亲和素-生物素复合体 用免疫过氧化物酶方法，RAP(RA，ras；P，多肽)单抗 明确表达增强的ras p21在大部分人结肠中的表达 和乳腺癌。浸润性乳腺癌强化 Ras-p21蛋白在肺癌中的表达普遍降低 原位、不典型增生和非典型增生。大多数人 纤维腺瘤和纤维囊性疾病引起的所有异常导管和小叶 患者均为阴性，正常乳腺和结肠上皮均为阴性。 检查过了。 我们还使用RAP单抗来定义ras p21蛋白在 结肠疾病状态的谱系。肿瘤的免疫组织化学分析 组织切片中的单个细胞显示ras p21的差异。 结肠癌与正常结肠上皮细胞表达的比较 良性结肠肿瘤和炎性或发育不良的结肠病变。我们的数据 Ras p21的表达与肿瘤的深度相关 在肠壁内，可能是结肠中相对较晚的事件 致癌。在高分化组中，ras p21的表达也增强。 前列腺癌和膀胱癌。 我们最近开发了ras p21的定量液体竞争RIA。 使用单抗Y13-259。通过使用纯重组ras p21的标准， 我们现在能够在调频水平上检测到p21，并确定 每个细胞的p21分子。定量RIA和RIA的同时使用 正常、发育不良和炎症性疾病的免疫组织化学分析 国家，以及癌症，应该导致更好地理解 Ras基因在这些病变发生中的作用。