- 作者: Peter Han-Chung Yee; Sai-Peng Sim
- 作者服務機構: Faculty of Medicine and Health Sciences, Universiti Malaysia Sarawak, Kuching, Sarawak, Malaysia
- 中文摘要: --
- 英文摘要:
Background: Nasopharyngeal carcinoma (NPC) is commonly found in Southern China and South
East Asia. Epstein-Barr virus (EBV) infection is well associated with NPC and has
been implicated in its pathogenesis. Moreover, various chromosome rearrangements
were reported in NPC. However, the underlying mechanism of chromosome
rearrangement remains unclear. Furthermore, the relationship between EBV and
chromosome rearrangement with respect to the pathogenesis of NPC has not been
established. We hypothesize that during virus- or stress-induced apoptosis,
chromosomes are initially cleaved at the base of the chromatin loop domain structure.
Upon DNA repair, cell may survive with rearranged chromosomes.
Methods: In this study, cells were seeded at various densities to induce apoptosis. Genomic
DNA extracted was processed for Southern hybridization. In order to investigate the
role of EBV, especially the latent membrane protein 1 (LMP1), LMP1 gene was
overexpressed in NPC cells and chromosome breaks were analyzed by inverse
polymerase chain (IPCR) reaction.
Results: Southern analysis revealed that high cell density resulted in cleavage of the mixed
lineage leukemia (MLL) gene within the breakpoint cluster region (bcr). This high
cell density-induced cleavage was significantly reduced by caspase inhibitor, ZDEVD-
FMK. Similarly, IPCR analysis showed that LMP1 expression enhanced
cleavage of the MLL bcr. Breakpoint analysis revealed that these breaks occurred
within the matrix attachment region/scaffold attachment region (MAR/SAR).
Conclusions: Since MLL locates at 11q23, a common deletion site in NPC, our results suggest a
possibility of stress- or virus-induced apoptosis in the initiation of chromosome
rearrangements at 11q23. The breakpoint analysis results also support the role of
chromatin structure in defining the site of chromosome rearrangement. - 中文關鍵字: --
- 英文關鍵字: --