CHROMOSOME ALTERATIONS AND PROTO-ONCOGENES TRANSPOSITION IN CARCINOGENESIS

致癌过程中的染色体改变和原癌基因转座

• 批准号: 3874689
• 负责人: N C POPESCU
• 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/3874689
• 关键词: Downs syndrome; HeLa cells; Papillomavirus; carcinogenesis; cervix neoplasms; chromosome disorders; chromosome translocation; gene expression; genetic mapping; growth factor receptors; keratin; myelogenous leukemia; natural gene amplification; neoplasm /cancer genetics; neoplasm /cancer invasiveness; nonhistone nucleoprotein; nucleic acid sequence; oncogenes; platelet derived growth factor; protooncogene; provirus; sex chromosomes; transfection; viral carcinogenesis; virus genetics

A human exocervical cell line that became tumorigenic after sequential transfection with human papillomavirus (HPV) 16 and an activated v-Ha-ras oncogene had HPV sequences on chromosome 21 near ets-2 proto-oncogene. HPV-16 insertion at this site was implicated in the formation of a homogeneously staining region, an alteration indicative of gene amplification that may be essential to the acquisition of cell immortality. HPVs associated with invasive cancer, adeno-12, Epstein-Barr, hepatitis-B and simian-40 viruses integrate at referential sites on the human genome. Fifty-one percent of 35 regionally localized integration sites of five DNA viruses correspond to the location of fragile sites and proto-oncogenes. Two proto-oncogenes, erbB-3 and dbl, two genes coding for nonhistone chromosomal protein, and a cluster of Cathepsin G-like genes were localized at regions of major interest on the human genome. ErbB-3 was mapped to chromosome 12qll-13 in close proximity to Int-1 and GLI proto-oncogenes. Dbl gene was localized on chromosome Xq27, a region that may be important for further defining the molecular alterations associated with chromosome fragility and X-linked mental retardation. HMG-14 and HMG-17 genes for nonhistone chromosomal protein were mapped on chromosomes 2lq22.3 and lp36.1, respectively. HMG-14 gene is located at the region considered critical for Down's syndrome. Cathepsin-G gene and a cathepsin G-like gene were mapped on chromosome 14 at band q11.2 near alpha and delta T-cell receptor gene, a site involved in most translocations in T-cell neoplasia.

一种人外分泌癌细胞系，在连续的 用人乳头瘤病毒（HPV）16和活化的v-Ha-ras转染 癌基因在21号染色体靠近ets-2原癌基因处有HPV序列。 HPV-16在该位点的插入与一种病毒的形成有关。 均匀染色区域，指示基因的改变 这可能是获得细胞永生所必需的。 与浸润性癌相关的HPV，腺病毒-12，EB病毒，乙型肝炎 而猿猴-40病毒整合在人类基因组的参考位点上。 五个DNA的35个区域定位整合位点中的51% 病毒对应于脆性位点和原癌基因的位置。 两个原癌基因erbB-3和dbl，两个编码非组蛋白的基因 染色体蛋白和一簇组织蛋白酶G样基因被定位 在人类基因组的重要区域。ErbB-3被映射到 染色体12 q11 -13与Int-1和GLI原癌基因非常接近。 Db 1基因定位于染色体Xq 27上，该区域可能是重要的 为了进一步确定与染色体相关的分子改变， 脆弱性和X连锁智力障碍。HMG-14和HMG-17基因 非组蛋白染色体蛋白定位在染色体2lq22.3上， lp36.1。HMG-14基因位于所考虑的区域 对唐氏综合症至关重要组织蛋白酶G基因和组织蛋白酶G样基因 定位于14号染色体上靠近α和δ T细胞的q11.2带 受体基因，一个参与T细胞瘤形成中大多数易位的位点。