Contribution of N-ras to metastasis of thyroid tumors

N-ras对甲状腺肿瘤转移的贡献

• 批准号: 6999073
• 负责人: CHANDREYEE DAS
• 金额: $ 4.21万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-30 至 2008-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6999073
• 关键词: biological signal transduction; cell differentiation; cell growth regulation; cell migration; cellular oncology; gene expression; gene interaction; genetic regulation; genetically modified animals; laboratory mouse; metastasis; neoplasm /cancer genetics; phenotype; postdoctoral investigator; protooncogene; retinoblastoma protein; thyroid neoplasm; tissue /cell culture

DESCRIPTION (provided by applicant): The tumor suppression activity of the retinoblastoma protein (pRb) is well established, as mutations in the retinoblastoma gene are associated with a wide variety of cancers. Tumor suppression by pRb is partly dependent on its role in differentiation, which is largely uncharacterized. Recently, the Ewen laboratory has shown that the Rb gene acts upstream of the N-ras proto-oncogene to regulate differentiation in mice. Furthermore, mice that are heterozygous for both Rb and N-ras develop thyroid adenomas that frequently metastasize. This proposal will study the genetic interaction between Rb and N-ras in parafollicular cells (C cells) of mice by measuring their metastatic potential as phenotype. The pathway by which N-ras loss contributes to metastasis is unknown, but it is thought that the migration of C-cell metastases may arise from aberrant expression of developmental Hox genes that cause C-cell migration in normal embryonic development. To understand the role of pRb and N-ras in metastasis, the effect of N-ras dosage on hox gene expression in pRb nullizygous metastases will be determined. Making the link between metastasis and embryonic development would be a valuable step in understanding malignant cancers.

描述（由申请人提供）：视网膜母细胞瘤蛋白（pRb）的肿瘤抑制活性已得到充分证实，因为视网膜母细胞瘤基因的突变与多种癌症相关。 pRb 的肿瘤抑制部分取决于其在分化中的作用，而这一作用在很大程度上尚未被表征。最近，Ewen 实验室表明，Rb 基因在 N-ras 原癌基因的上游发挥作用，调节小鼠的分化。此外，Rb 和 N-ras 杂合的小鼠会出现经常转移的甲状腺腺瘤。该提案将通过测量小鼠滤泡旁细胞（C 细胞）的转移潜力作为表型来研究 Rb 和 N-ras 之间的遗传相互作用。 N-ras 缺失导致转移的途径尚不清楚，但认为 C 细胞转移的迁移可能是由于发育性 Hox 基因的异常表达引起的，该基因导致正常胚胎发育中的 C 细胞迁移。为了了解 pRb 和 N-ras 在转移中的作用，将确定 N-ras 剂量对 pRb 无效转移中 hox 基因表达的影响。建立转移和胚胎发育之间的联系将是了解恶性肿瘤的重要一步。