Genetic Alternations In EBV-infected Breast Cancer Cell Lines

• Main Authors: Hsiang-yi Wu, 吳香儀
• Other Authors: Jin-Yuh Shew
• Format: Others
• Language: zh-TW
• Published: 2003
• Online Access: http://ndltd.ncl.edu.tw/handle/48252364424495691500

碩士 === 國立臺灣大學 === 生物化學暨分子生物學研究所 === 91 === Breast cancer is the most common fatal malignancy cancer of females in developed countries. From 1970 to 1990, breast cancer is an important cancer of women in Taiwan and the incidence of age in breast cancer trends to early onset. The etiology of breast cancer involves a complex interplay of genetic, hormonal, and dietary factor that are superimposed on the physiological status of the host. At the molecular level, several oncogenes and tumor suppressor genes were shown to be involved in the development of breast cancer. At 1995, EBV was first detected in human breast cancers then several reports further indicated the presence of EBV in the 20%-50% breast tissue. So our laboratory is interested in developing effective analysis to examine the existence of Epstein-Barr virus（EBV）genome and gene product(s) in breast cancer specimens from Taiwan. We want to know what is the role of EBV in breast cancer carcinogenesis. Some reports indicate that one of the EBNA-1 associated cellular protein ,p32/TAP, was important for RNA splicing. Therefore, we propose a hypothesis that through EBNA-1 and p32/TAP interaction, EBV may enhance the relaxation of RNA fidelity of the host cell. Then the consequent result may cause the mutation of TSG101 and ERα (estrogen receptor alpha). In order to test this hypothesis, we compare the mutation frequency of TSG101 and ERα between parental and EBV-infected breast cancer cell lines and some other cancer cell lines. We also want to know wheather EBV will affect the cellular gene(s) in DNA level .Therefore, the status of p53 between parental and EBV-infected cells has been analyzed as well. Our results pointed out that increase of TSG101 aberrant splicing transcripts has been found in EBV-infected HBL-100-A,T47D-A and A431-A cells. In addition, our result indicated that increase of ERα alternative splicing transcripts has been found in these EBV-infected cells. These data strongly support the hypothesis that EBNA-1 and p32/TAP interaction, EBV may enhance the relaxation of RNA fidelity of the host cell. Then the consequent result may cause the mutation of TSG101 and ERα. According to this excited discovery, the inter-relationship of EBV and those genetic alterations will provide important clues to elucidate the possible role of EBV in carcinogensis although the p53 status has not been affected after EBV infection. Our results pointed out that EBV might involve in breast cancer progression. However, many other mechanistic aspects underlying EBV-mediated transcription are still unclear. For instance, how EBV promotes cellular proliferation through TSG101 and ERα? What specific regulatory genes are involved in this growth pathway? What EBV-stimulated cell cycle signal transduction pathways are important in breast carcinogenesis? Are some of the questions remain to be addressed ?