权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Molecular cloning of cervical cancer tumor suppressor gene

宫颈癌抑癌基因的分子克隆

基本信息

批准号：
06454185
负责人：
YUTSUDO Masuo
金额：
$ 4.54万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1996
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-06454185/
关键词：
cervical cancer tumor suppressor gene human papillomavirus 子宮頸癌癌抑制遺伝子

项目摘要

Although cervical carcinoma is caused by infection with certain types of human papillomavirus (HPV) such as types 16 and 18, expression of the E6E7 oncogenes of these HPV is not sufficient for the carcinogenesis. In addition to it, inactivation of some tumor suppressor gene (s) may be indispensable. The objective of this research is to isolate tumor suppressor genes involved in cervical carcinogenesis.We attempted to isolate a gene (s) affecting tumorigenesity of cervical carcinoma-derived cell line (CGL4) by expression cloning using cDNA library prepared from normal human fibroblasts, and obtained a candidate tumor suppressor gene AF337. This gene suppressed growth of tumorigenic CGL4 cells when introduced, that is, AF337 expression vector gave smaller number of drug resistant colonies than control vectors, and almost (23/24), except one (clone 5), colonies appeared did not retain or express the cDNA.The clone 5 formed tumors in nude mice, but the 2 of 3 tumors formed lost the cDNA.The AF337 mRNA was about 2.3kb in size and was expressed in all tissues examined. Expression of this gene was reduced in some cancer cell lines. The predicted gene product was composed of 373 amino acids and possessed highly acidic region, proline-rich domain, and leucine-zipper motif, suggesting that AF337 may be a transcription factor. This gene had no apparent sequence homology with other genes of known function.

尽管宫颈癌是由某些类型的人乳头瘤病毒（HPV）（例如 16 型和 18 型）感染引起的，但这些 HPV 的 E6E7 癌基因的表达不足以致癌。除此之外，某些抑癌基因的失活可能也是必不可少的。本研究的目的是分离参与宫颈癌发生的抑癌基因。我们尝试利用正常人成纤维细胞制备的cDNA文库进行表达克隆，分离影响宫颈癌衍生细胞系（CGL4）致瘤的基因，获得候选抑癌基因AF337。该基因引入后抑制了致瘤CGL4细胞的生长，即AF337表达载体产生的耐药集落数量比对照载体少，并且除了1个（克隆5）之外，几乎（23/24）出现的集落不保留或表达cDNA。克隆5在裸鼠中形成肿瘤，但形成的3个肿瘤中的2个丢失了cDNA。AF337 mRNA约为大小为 2.3kb，在所有检查的组织中都有表达。该基因的表达在某些癌细胞系中降低。预测的基因产物由373个氨基酸组成，具有高酸性区域、富含脯氨酸的结构域和亮氨酸拉链基序，表明AF337可能是一种转录因子。该基因与其他已知功能的基因没有明显的序列同源性。