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

TSC403基因是一种致癌基因，最近被发现是肺特异性的，与影响癌细胞转移的溶酶体膜糖蛋白(lamp)- 1,2具有同源性。在妇科肿瘤中检测TSC403基因的改变。宫颈癌40例中有19例、子宫内膜癌29例中有3例（48%）、卵巢癌33例中有3例（9%）存在TSC403基因mRNA过表达。在29个例子中33个例子中。Southern-blot杂交未发现TSC403基因扩增或重排。TSC403基因mRNA在子宫癌细胞系中也有过表达，5株细胞系中有2例（40%）检测到TSC403基因mRNA过表达。构建了将TSC403基因mRNA纳入表达载体的基因构建，并在不表达TSC403基因mRNA的子宫颈细胞系中获得了转化。该方法使TSC403基因在体外和体内的功能分析成为可能。HPV的E6癌蛋白与p53蛋白相互作用，被认为在HPV致宫颈癌的过程中起主要作用。p53基因具有天然多态性，编码脯氨酸（p53Pro）或精氨酸（p53Arg）。据报道，p53Arg比p53Pro更容易受到E6介导的降解。我们分析了这种多态性是否与宫颈癌的高危因素有关。81例宫颈癌中Arg和Pro的比值为0.54:0.30:0.16，对照组329例为0.42:0.47:0.11。宫颈癌组p53Arg纯合子频率较高。提示p53codon72多态性模式成为癌症的高危因素。然而，在一般人群中，p53Arg纯合子的频率为40%，p53Arg本身并不代表宫颈癌的特定风险标志，需要包括其他风险因素的分析。少

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