HUMAN 3P RECESSIVE ONCOGENES

描述(改编自《调查者摘要》)：这是一个新的 关于鉴定和研究一种可能的隐性肿瘤的建议 3p21.3中一个或多个抑制基因在肺发育中的重要作用 癌症。这种肿瘤抑制因子的证据来自于研究表明 创业前期3p21等位基因缺失和3p基因缺失 在70-80%的小细胞和非小细胞肺癌中。具体而言 目的1利用一系列资源克隆该基因，包括 肺癌细胞系中一组定义350kb和350kb的纯合缺失 潜在30kb的临界区，以及高分辨率的物理和 该区域已鉴定出25个cdna克隆的转录图谱。 具体目标2是通过以下方式确定该基因座的功能特征 3p染色体部分基因导入人肺癌细胞系的研究 携带3p21.3异常，并检测致瘤性抑制 采用裸鼠、软琼脂培养和细胞凋亡研究。具体而言 目标3申请人计划跟进一项观察结果，即该区域 可能通过研究参与抑制端粒酶活性 肺癌细胞端粒长度和端粒酶功能的基因改变 调职。

DESCRIPTION (Adapted from the Investigator's Abstract): This is a new proposal to identify and study the function of a putative recessive tumor suppressor gene or genes in 3p21.3 important in the development of lung cancers. Evidence for such a tumor suppressor comes from studies showing the early loss of 3p21 alleles in preneoplasia, and allele loss of 3p genes in 70-80% of both small cell and non-small cell lung cancers. In specific aim I it is proposed to clone the gene using a series of resources including a set of homozygous deletions in lung tumor cell lines defining a 350 kb and potentially 30 kb critical region, and a high resolution physical and transcription map with 25 cDNA clones already identified in this region. Specific aim 2 is to determine functional characteristics of this locus by introduction of portions of chromosome 3p into human lung cancer lines bearing a 3p21.3 abnormality, and testing for suppression of tumorigenicity using nude mice, soft agarose culture and studies of apoptosis. In specific aim 3 the applicant plans to follow up on an observation that this region might be involved in suppressing telomerase activity by investigating telomere length and telomerase function in lung cancer cells altered by gene transfer.