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ROLE OF LOSS OF THE SHORT ARM OF CHROMOSOME 3 IN HUMAN ORAL SQUAMOUS CELL CARCINIGENESIS

3号染色体短臂缺失在人类口腔鳞状细胞癌变中的作用

基本信息

批准号：
09672038
负责人：
NEGISHI Akihide
金额：
$ 2.3万
依托单位：
TOKYO MEDICAL AND DENTAL UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09672038/
关键词：
ORAL CANCER SQUAMOUS CELL CARCINOMA GENETICS CHROMOSOME 3 MICROCELL FUSION TUMOR SUPPRESSOR GENE

项目摘要

Cytogenetic and restriction fragment length polymorphism (RFLP) analyses have suggested that a putative tumor suppressor gene(s), which may play an important role in the development of human oral squamous cell carcinoma (SCC), is located on the short arm of chromosome 3 (3p). We previously reported that introducing an intact human chromosome 3 into three different oral SCC tumorigenic cell lines completely suppresses the tumorigenicity of each cell line with significant decrease in the in vitro growth rate and morphological changes. To map the tumor suppressor gene(s) on 3p, we have now examined the tumorigenicity of microcell hybrid clones which contain various fragments derived from 3p that were introduced via microcell-mediated chromosome transfer. Sixteen hybrid clones were obtained from four successful experiments and these clones were classified into two groups four fully tumorigenic clones and 12 suppressed phenotype clones. Analyses of the 3p segments in the series of hybrid clones using RFLP or microsatellite markers revealed that the 3p21.2-p2l.3 and/or 3p25 regions were consistently retained in the 12 clones with suppressed phenotype, but not in the four tumorigenic clones. The more proximal 3pl3 regions was also retained in three non-tumorigenic clones. The overall results are fairly compatible with the recent data that there are three discrete regions on 3p showing frequent allelic losses in oral SCC, and directly provide functional evidence for the presence of tumor suppressor genes for oral SCC in these regions. The possibility that three genes, FHIT, VHL, and TbetaR-II recently identified on 3p may be significantly involved in oral SCC development is also discussed.

细胞遗传学和限制性片段长度多态性分析表明，一个可能在口腔鳞状细胞癌发生发展中起重要作用的抑癌基因(S)位于3号染色体(3p)的短臂上。我们先前报道，将完整的人类3号染色体导入三种不同的口腔鳞状细胞癌致瘤细胞系中，可以完全抑制每种细胞系的致瘤性，并显著降低体外生长速度和形态变化。为了将肿瘤抑制基因(S)定位在3P上，我们现在检测了含有来自3P的各种片段的微细胞杂交克隆的致瘤性，这些片段是通过微细胞介导的染色体转移引入的。从4次成功的实验中获得了16个杂交克隆，这些克隆被分为两组，4个完全致瘤克隆和12个表型抑制克隆。用RFLP或微卫星标记对一系列杂交克隆中的3p片段进行分析，结果表明，在12个表型抑制的克隆中，3p21.2-p21.3和/或3p25区域一致保留，而在4个致瘤克隆中则没有。在3个非致瘤克隆中也保留了更近端的3pl3区域。总体结果与最近的数据相一致，即口腔鳞癌在3P上存在三个离散区域，显示频繁的等位基因丢失，并直接为这些区域存在口腔鳞癌的抑癌基因提供了功能证据。还讨论了最近在3p上发现的三个基因FHIT、VHL和TbetaR-II可能与口腔鳞状细胞癌的发生密切相关。