| Summary: | 碩士 === 長庚大學 === 基礎醫學研究所 === 88 === Latent membrane protein (LMP1) is a major protein expressed in Epstein-Barr virus (EBV)-associated tumors such as nasopharyngeal carcinoma (NPC), B-lymphoma and T-lymphoma. LMP1 has been considered oncogenic. According to its origin of isolation and sequence polymorphisms, LMP1 can be classified into two forms. NLMP1 is derived from NPC biopsy tissue while BLMP1 is identified in a B cell line, B95-8. NLMP1 is able to transform BALB/c 3T3 cells and subcutaneous implantation of such cells into nude mice can induce the growth of a tumor. BMPL1, on the other hand, shows no such effect. However, the role of NLMP1 in carcinogenesis is not clear.
In this study, NLMP1 transgenic mice were used as an in vivo animal model to investigate the role of NLMP1 in carcinogenesis. As a result, NLMP1 was detected in organs such as skin, heart, liver and testis. Moreover, the epithelial cells of the NLMP1 transgenic mice showed an increased degree of hyperplasia and undifferentiation as the mice aged. Nevertheless, no tumor growth was observed in any case.
A two-stage carcinogenesis method was designed to further investigate how NLMP1 is involved in carcinogenesis. To serve this purpose, a tumor initiator DMBA and a tumor promoter TPA were applied to the skin of the experimental mice which were the offsprings of NLMP1 transgenic mice (line 50). The experimental mice were divided into three groups: the homozygotes, the heterozygotes and the littermates; the last group carries no NLMP1 gene. At the first stage, at week 0, DMBA (30mg /150ml acetone) was applied to mice in all three groups. A week after the first treatment, at the second stage, mice were either untreated or treated with TPA (5mg/150ml acetone) over a period of 5 weeks or 15 weeks. Comparisons were then made on the size, the growth rate and the induction rate of papillomas to evaluate the effect of NLMP1. For mice treated with DMBA/TPA, papillomas appeared on the homozygote group a week earlier than the littermate group. Furthermore, papillomas, which were observed on the homozygote group treated with TPA over a period of 15 weeks grew faster than other groups before week 10. Such difference, however, was no longer significant after week 10. The number and the induction rate of papillomas observed on mice treated with TPA over 15 weeks were significantly greater than the 5-week group. For the DMBA control, papillomas were observed on homozygote group after week 30, and observed on 100% of mice at week 50, while the littermate group showed no sign of papillomas throughout the experiment. These results suggest that NLMP1 likely involved in carcinogenesis as a tumor promoter.
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