MOLECULAR GENETIC STUDIES OF METASTASIS IN LUNG CANCER

肺癌转移的分子遗传学研究

• 批准号: 3190780
• 负责人: GEORGE D. SORENSON
• 金额: $ 15.85万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-02-01 至 1992-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3190780
• 关键词: DNA; athymic mouse; fibroblasts; gene dosage; gene expression; genetic models; human tissue; laboratory mouse; metastasis; model design /development; neoplasm /cancer genetics; nucleic acid sequence; small cell lung cancer; transfection

Small cell carcinoma of the lung (SCCL) is a common form of lung cancer and less than 5% of patients with this type of carcinoma survive more than five years. A major reason for the dismal prognosis with SCCL is that this tumor metastasizes early and widely. Since SCCL is an highly metastatic tumor, it was selected as an extremely appropriate prototype for determining the genetic basis for the metastatic phenotype in human cancer. The goal of this proposal is to investigate an experimental model of spontaneous metastases from subcutaneous tumors in nude mice induced by NlH/3T3 cells transfected by genomic DNA from a cell line established from metastatic human small cell carcinoma of the lung (SCCL). Metastases are rapidly produced in this model and preliminary studies indicate the presence of human sequences in the cells of the pulmonary metastases. It is hypothesized that these human sequences represent genes which are etiologically related to the metastatic phenotype expressed by these cells. It is anticipated that these investigations will provide significant amounts of important new information and provide a better understanding of the mechanisms of metastases from human malignant tumors. The specific aims are: 1. To determine whether transfection with DNA from metastatic SCCL obtained directly from a patient will induce NIH/3T3 and normal fibroblasts to develop the metastatic phenotype. 2. To identify the human sequences present in the transfected metastatic NIH/3T3 cells and investigate their biological activity. 3. To evaluate factors which may influence the incidence of pulmonary metastases in the nude mice based upon the identification of the human sequences (gene or genes) in the metastatic cells.

肺的小细胞癌（SCCL）是肺的常见形式 癌症和不到5％的这种癌患者 生存超过五年。 令人沮丧的主要原因 SCCL的预后是这种肿瘤早期转移 广泛。 由于SCCL是高度转移性肿瘤，因此被选择 作为确定遗传的极其适当的原型 人类癌症转移表型的基础。 该建议的目的是研究实验模型 裸鼠皮下肿瘤的自发转移 由基因组DNA从细胞转染的NLH/3T3细胞诱导 从转移性人类小细胞癌建立的线 肺（SCCL）。 转移是在此模型中迅速产生的，并且 初步研究表明在 肺转移的细胞。 假设这些 人类序列代表与病因相关的基因 这些细胞表达的转移表型。 这是 预计这些调查将提供重要的 大量重要的新信息，并提供更好的 了解人类恶性转移的机制 肿瘤。 具体目的是： 1。确定是否从转移性SCCL转染DNA 直接从患者获得的将诱导NIH/3T3和正常 成纤维细胞开发转移表型。 2。确定转染中存在的人类序列 转移性NIH/3T3细胞并研究其生物学活性。 3。评估可能影响发生率的因素 裸鼠中的肺转移 鉴定人类序列（基因或基因） 转移细胞。