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Title: | EB病毒感染霍金氏淋巴癌會抑制p21cip1/waf1的表現並導致較差的預後 EBV-positive Hodgkin lymphoma is associated with suppression of p21cip1/waf1 and a worse prognosis |
Authors: | Ting-Yun Liu 劉亭勻 |
Advisor: | 林中梧(Chung-Wu Lin) |
Keyword: | 霍金氏淋巴癌,預後, Hodgkin lymphoma,EBV,EBER1,p21cip1/waf1,prognosis, |
Publication Year : | 2010 |
Degree: | 博士 |
Abstract: | 中文摘要
大約有30~50%的霍金氏淋巴癌感染EB病毒,但對於感染EB病毒在臨床上對疾病的發展結果之影響仍未釐清。EB病毒轉錄的小片段RNAs (EBERs)出現在所有被EB病毒感染的疾病當中,但關於它們的功能仍未知。 將EBER1轉染至兩株霍金氏淋巴癌細胞株,KM-H2和L428,並以微陣列方式分析被EBER1誘導之基因改變。我們在霍金氏淋巴癌細胞株中發現EBER1會抑制p21cip1/waf1的表現;另外,p21cip1/waf1的正調控因子,如p53,EGR1,和STAT1也會受到抑制。在霍金氏淋巴癌細胞株中,p21cip1/waf1的表現會受到EBER1抑制,並對histone deacetylase inhibitors 和 proteasome inhibitors這兩種已知會誘導p21cip1/waf1 表現的藥物所引發的細胞凋亡具有抵抗性是具有相關性。根據分析臨床上的檢體,發現感染EB病毒的霍金氏淋巴癌其p21cip1/waf1和活化之caspase 3的表現較弱。臨床數據分析顯示,感染EB病毒的霍金氏淋巴癌之抑制p21cip1/waf1的表現,會有一個較差的兩年存活率(EB病毒感染霍金氏淋巴癌有45%存活率,相對應於未感染EB病毒霍金氏淋巴癌有77%存活率,p = 0.002)。 雖然EBER1抑制p21cip1/waf1表現的機制仍未釐清,但EBER1會抑制p21cip1/waf1的轉錄並且經由抑制p53,EGR1,和STAT1而對細胞凋亡具有抵抗性。EBER1具有抵抗細胞凋亡的能力,對於避免Reed-Sternberg cells對藥物產生的細胞凋亡以及感染EB病毒之霍金氏淋巴癌的臨床表現可能是很重要的。 Abstract About 30-50% of Hodgkin lymphomas (HLs) harbor the Epstein-Barr virus (EBV), but the impact of EBV infection on clinical outcomes has been unclear. EBV-encoded small RNAs (EBERs) are present in all EBV-infected cells, but their functions are still unknown. EBER1 was transfected into two HL cell lines, KMH2 and L428, and microarrays were used to screen for EBER1-induced changes. We found that EBER1 suppressed p21cip1/waf1 transcription in HL cell lines. In addition, positive regulators of p21cip1/waf1 transcription, such as p53, EGR1, and STAT1, were decreased. Suppression of p21cip1/waf1 in the EBER1 |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/22833 |
Fulltext Rights: | 未授權 |
Appears in Collections: | 病理學科所 |
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