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Detection of TSC alteration and molecular risk factor in cervical cancer.

Detection of TSC alteration and molecular risk factor in cervical cancer.
宫颈癌 TSC 改变及分子危险因素检测。
批准号:
11671617
负责人:
FUJITA Masami
金额:
$2.37万
依托单位:
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (C)
财政年份:
1999
资助国家:
日本
项目状态:
已结题
起止时间:
1999 至 2000

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中文摘要
翻译
TSC 403基因是癌基因,其最近被鉴定为肺特异性的,并且与影响癌细胞转移的溶酶体膜糖蛋白(lamp)-1,2具有同源性。检测妇科肿瘤组织中TSC 403基因的改变。40例宫颈癌中19例、29例子宫内膜癌中3例(48%)、33例卵巢癌中3例(9%)检测到TSC 403基因mRNA过表达。在33个例子中的29个例子中。Southern杂交未检测到TSC 403基因的扩增或重排。TSC 403基因的mRNA过表达也在子宫颈癌细胞系中进行了分析,并在5个细胞系中的2例(40%)中检测到。制备了将TSC 403基因mRNA包含在表达载体中的基因构建体,并且从不表达TSC 403基因mRNA的子宫颈癌细胞系获得了表达载体。 ...更多信息 HPV E6癌蛋白与p53蛋白相互作用,在HPV致宫颈癌中起重要作用。p53基因具有天然多态性,编码脯氨酸(p53 Pro)或精氨酸(p53 Arg)。据报道,p53 Arg比p53 Pro更容易受到E6介导的降解。分析该多态性是否与宫颈癌的高危因素有关。81例宫颈癌患者血清中Arg、Pro的比值为0.54:0.30:0.16; 329例正常人血清中Arg、Pro的比值为0.42:0.47:0.11。p53 Arg纯合子在宫颈癌组中的频率较高。提示p53 codon 72多态性模式可能成为胃癌的高危因素。但p53 Arg纯合子在普通人群中的频率为40%,单独p53 Arg不能作为宫颈癌的特异性危险标志物,还需要对其他危险因素进行分析。少
英文摘要
A TSC403 gene is the oncogene, which is recently identified as lung specific, and has homology with Lysosomal Membrane glycoproteins (lamps)-1, 2 which influences the metastasis of the cancer cell. The alteration of TSC403 gene was examined in the gynecological tumor. TSC403 gene mRNA overexpression was detected in 19 cases of 40 cases of uterine cervical cancer, 3 cases of 29 cases (48%) of uterine endometrial cancer and 3 cases of 33 cases (9%) of ovarian cancer. during 29 examples during 33 examples. The gene amplification or re-arrangement of the TSC403 gene was not detected by Southern-blot hybridization. The mRNA overexpression of the TSC403 gene was also analyzed in uterine cervical cancer cell lines, and detected in 2 cases of 5 cell lines (40%). The gene construct that a TSC403 gene mRNA was included into the expression vector was made, and the transformant was obtained from the uterine cervical cancer cell lines which does not express TSC403 gene mRNA.A functional analysis of … More the TSC403 gene became possible by this in vitro and in vivo.The E6 oncoproptein of HPV interact with the p53 protein, and it is thought that it play a major role in the carcinogenesis of cervical cancer by HPV.The p53 gene has a natural polymorphism, encoding either proline (p53Pro) or Arginine (p53Arg). It was reported that p53Arg was more susceptible to E6 mediated degradation than the p53Pro. We analyzed whether this polymorphism were concerned with the high risk factor of cervical cancer. The ratio of Arg and Pro was 0.54 : 0.30 : 0.16 in the 81 cases of cervical cancer and 0.42 : 0.47 : 0.11 in 329 cases of control. The frequency of p53Arg homozygotes was statistically high in the cervical cancer group. It is suggested that the pattern of p53codon72 polymorphism became the high risk factors of cancer. However, the frequency of p53Arg homozygotes is 40% in general population, p53Arg alone does not represent a specific risk marker for cervical cancer and an analysis including other risk factors should be was necessary. Less
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