Genetic Analysis of the Type II TGF-beta Receptor(RII) Gene at 3p22 in Cervical Cancer

• Main Authors: LAI, CHIEN-HSUN, 賴建勳
• Other Authors: Chao Chung-Faye
• Format: Others
• Language: zh-TW
• Published: 1997
• Online Access: http://ndltd.ncl.edu.tw/handle/76576083963844712536

碩士 === 國防醫學院 === 生物及解剖學研究所 === 86 === Carcinoma of the uterine cervix is the most prevalent cancer of women in Taiwan, and the second prevalent cancer globally. The major cause of this mal ignancy has been imputed to cervical infection with highrisk types of human pa pillomavirus(HPV). However, HPV infection alone is not sufficient for full car cinogenesis, suggesting the requirement of additional genetic events. Based on previous assay of loss of heterozygosity(LOH) on cervical cancer tissues, chr omosomal region 3p22-24 was found with high LOH frequency of 44%, pointing th e location of tumor suppressor genes. The type II TGF-beta receptor (RII) gene , located at 3p22, playsa critical role in cell differentiation of kerationcyt e and has been showed to be a tumor suppressor gene in gastric and colon cance r which,in most cases, replication error (RER) type mutation. purpose of this study is to analyze the genetic alteration of RII gene in cervical cancer. Fif teen squamous cell carcinoma (SCC) of the cervix,which showed either LOH at 3p 22-24 or microsatellite RER, and six squamous cell carcinoma cell lions were s tudied. Using PCR-SSCP and DNA sequencing analysis, we found an internal delet ion (exon 2 to 6) in ME180 cell and truncated deletion (exon 7) in HeLa cell.I n tumor and normal tissues, two polymorphism at intron 2 and exon 4 were foun d, but no mutation was found at the RER "hotspot" of poly A10 tract or other e xons. Comparing our sequence with the reported RII cDNA sequence, cloned from a human HepG2 cell, the latter harborstwo point mutation at exon 5 and 3'UTR. We concluded that RII gene is frequently deleted in cervical cancer cell lines , but is rarely mutated incervical cancer tissues. Mutation at either the non- codingregion of RII or at other unidentified tumor suppressor gene is responsi ble for the frequent 3p22-24 LOH of cervical cancer.