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

• Project/Area Number: 11671617
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Osaka University
• Principal Investigator: FUJITA Masami Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (60303963)
• Co-Investigator(Kenkyū-buntansha): 榎本 隆之 大阪大学, 医学系研究科, 助手 (90283754)
• Project Period (FY): 1999 – 2000
• Project Status: Completed (Fiscal Year 2000)
• Budget Amount: ¥3,700,000 (Direct Cost: ¥3,700,000); Fiscal Year 2000: ¥800,000 (Direct Cost: ¥800,000); Fiscal Year 1999: ¥2,900,000 (Direct Cost: ¥2,900,000)
• Keywords: TSC403 / cancer / cervix / oncogene / HPV / p53 / TSC40

Research Abstract

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 the TSC403 gene became possible by this in vitro and in vivo.
The E6 oncopro
ptein 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.