IDENTIFICATION OF MOLECULAR MARKERS FOR HUMAN LUNG CANCER

人类肺癌分子标记物的鉴定

• 批准号: 5201580
• 负责人: J A LAUTENBERGER
• 金额: --
• 依托单位: DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS
• 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/5201580
• 关键词: biomarker; gene expression; genetic mapping; human genetic material tag; human tissue; hybrid cells; in situ hybridization; lung neoplasms; messenger RNA; neoplasm /cancer diagnosis; neoplasm /cancer genetics; neoplastic cell; oncogenes; oncoproteins; open reading frames; prognosis; protein structure function; tissue /cell culture

We have used the differential display method to isolate a novel gene, N8, which expresses a 2.4 Kb mRNA at higher levels in lung tumor cells than normal cells. N8 mRNA contains a 552 nucleotide open reading frame (ORF) which encodes a 184 amino acid protein. In kidney, we have identified a larger ORF (N8L) encoding a 248 amino acid protein which has an extra 64 amino acids immediately to the N-terminal of N8 protein. Using somatic cell hybrid panel and fluorescence in situ hybridization (FISH) techniques, we have localized the N8 gene to human chromosome 8q13 region. N8 mRNA is present at high levels in human adult kidney, brain, small intestine, prostate, and pancreas. It is expressed at moderate levels in adult colon and placenta, and at low levels in several other tissues, including lung. The N8 gene is specifically expressed in the gut, nasal epithelia, areas surrounding eyes, and salivary glands in either 18 day-old embryo or one day-old newborn mice, suggesting the N8 gene may be developmentally regulated and may play different roles during embryogenesis and in adult stage. N8 protein is a hydrophilic, cytoplasmic protein capable of forming homodimers. N8 protein is present at very high levels in lung tumor cell lines and very low levels in normal lung tissue-derived cell lines. It is also present in many other tumor cell lines, including breast, colon, prostate, and brain cancer and leukemia cell lines. N8 protein has limited homology to some cytoskeleton-related proteins, such as myosin heavy chain, microtubule-vesicle linker CLIP-170, US01 intracellular transport protein and intermediate filament-associated protein restin. N8 could be used as a potential molecular marker for lung cancer.

我们用差异显示的方法分离了一个新的基因N8， 在肺肿瘤细胞中表达2.4kb的mRNA水平高于 正常细胞。N8基因包含一个552个核苷酸的开放阅读框架(ORF) 编码184个氨基酸的蛋白质。在肾脏方面，我们已经确定 一个较大的ORF(N8L)，编码248个氨基酸的蛋白质，有一个额外的 氨基酸的N端立即到N8蛋白。vbl.使用 体细胞杂交板与荧光原位杂交 技术，我们已经将N8基因定位在人类染色体8q13上 区域。N8基因在成人肾脏、脑、 小肠、前列腺和胰腺。它是以中等表达的 在成人结肠和胎盘中的水平，以及在其他几个组织中的低水平 组织，包括肺。N8基因特异性地表达在 肠道、鼻上皮、眼周围区域和唾液腺 无论是18天大的胚胎还是一天大的新生小鼠，都表明是N8 基因可能在发育过程中受到调节，并可能在不同的过程中发挥不同的作用 胚胎发育和成虫期。N8蛋白是一种亲水性的， 能够形成同源二聚体的细胞质蛋白。存在N8蛋白 在肺癌细胞系中含量很高，而在肺癌细胞系中含量很低 正常肺组织来源的细胞系。它也存在于许多其他 肿瘤细胞系，包括乳腺癌、结肠癌、前列腺癌和脑癌，以及 白血病细胞系。N8蛋白的同源性仅限于 细胞骨架相关蛋白，如肌球蛋白重链， 微管-囊泡连接物CLIP-170，US01细胞内转运蛋白 和中间细丝相关蛋白restin。可以使用N8 作为肺癌的潜在分子标记物。