Egf Receptor in Normal and Cancerous Intestinal Biology

正常和癌性肠道生物学中的 Egf 受体

• 批准号: 6368720
• 负责人: DAVID W. THREADGILL
• 金额: $ 27.13万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-06-01 至 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6368720
• 关键词: chemical carcinogen; chemical carcinogenesis; colorectal neoplasms; epidermal growth factor; gastrointestinal system; gene targeting; genetically modified animals; growth factor receptors; laboratory mouse; protein structure function; receptor expression

DESCRIPTION (provided by applicant): The epidermal growth factor receptor (Egfr) is a transmembrane receptor tryrosine kinase that is required in numerous tissues during development and is associated with many forms of cancer. From mouse knockout studies, the Egfr is known to be required for the maturation and/or maintenance of the mature intestinal tract. Furthermore, genetic evidence suggests that the Egfr is required during colorectal tumorigenesis. This is despite that fact that the gene encoding Egfr is not known to be mutated during colorectal cancer development. Although cancer of the colon and rectum is the third most frequently diagnosed cancer in the United States and accounts for the second largest number of cancer deaths, the role of only a few genes has been studied in detail; these genes are typically mutated during colorectal tumorigenesis or are associated with familial forms of the disease. Little is know about genes that appear to be required for the progression of tumorigenesis but do not become mutated themselves like Egfr. The objectives of the proposed research are therefore (1) to investigate the global importance of Egfr during development of colorectal cancer, (2) to determine the temporal requirement for Egfr during colorectal cancer development, (3) to define the mode of action of Egfr during tumorigenesis, and (4) to investigate the function of Egfr in non-epithelial compartments of the gastrointestinal tract.

性状（由申请人提供）：表皮生长因子受体 （Egfr）是一种跨膜受体酪氨酸激酶， 许多组织在发展过程中，并与许多形式的 癌从小鼠基因敲除研究中，已知Egfr是细胞增殖所必需的。 成熟和/或维持成熟的肠道。此外，委员会认为， 遗传学证据表明，在结直肠癌的发生过程中， 肿瘤发生尽管事实上编码Egfr的基因不是 已知在结直肠癌发展过程中发生突变。虽然癌症 结肠和直肠是世界上第三大最常诊断的癌症。 美国和占第二大癌症死亡人数， 只有少数基因的作用已经详细研究;这些基因通常是 在结直肠肿瘤发生过程中突变或与家族性形式相关 疾病。人们对这些基因知之甚少， 肿瘤发生的进展，但不会像Egfr一样自身突变。 因此，拟议研究的目标是（1）调查 EGFR在结直肠癌发展过程中的全球重要性，（2） 确定结直肠癌期间Egfr的时间需求 （3）确定Egfr在肿瘤发生过程中的作用方式， (4)为了研究EGFR在非上皮区室中的功能， 胃肠道