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Amplification-driven BCL6 overexpression in urothelial carcinoma of urinary bladder

Urinary bladder urothelial carcinoma is the most common cancer of the urinary
tract. About 70% of the diagnosed tumors classified as Non-invasive tumor, which is
usually multiple. Despite surgical removal and perioperative chemotherapy, tumor
recurrence is not uncommon. However, the chance for such non-invasive tumors to
advance to the muscle-invasive stage is relatively small and the 5-year survival rate
approaches 95%. The rest 30% are classified as invasive tumors which usually pursue
aggressive clinical course. In spite of radical cystectomy in conjunction with
debilitating chemotherapy and/or radiotherapy, more than 50% of invasive tumors
eventually spread to distant organs. The 5-year survival rate for patients with distant
metastasis is only about 6%. The current challenge in the management of urinary
bladder carcinoma is the lack of powerful prognostic marker and promising therapeutic
agents. Accordingly, to identify novel biomarks to adjust therapeutic strategy is
mandatory. The BCL6 proto-oncogene encodes a nuclear transcriptional repressor, it¡¦s
inhibits DNA repair pathways and TP53. Perturbation of both these pathways may
contribute to normal cell function by repressing DNA damage responses and permitting
somatic hypermutation but , in the context of malignancy, this could lead to mutations
promoting aggressive tumor. Several studies have demonstrated that BCL6 play a role in
different cancer types, however, the function of BCL6 in bladder cancer is understood.
Therefore, in this study, we will analyze the endogenous BCL6 mRNA and
total/activated BCL6 protein in various bladder cancer cell lines, including BFTC905,
and J82. Then we will knockdown of the BCL6 gene by shRNA interference and
analyze how it implicates various cellular processes essential to cancerous states. And
then we will be analyzed the affection of cell survival, migration and invasion.
Conversely, Overexpression of BCL6 in bladder cancer cell lines will be assessed cell
proliferation, migration and invasion. Finally, studying it¡¦s affection in vivo. We
demonstrate that BCL6 is correlated with bladder cancer.

Identiferoai:union.ndltd.org:NSYSU/oai:NSYSU:etd-0810112-224956
Date10 August 2012
CreatorsWu, Wen-Ren
Contributorsnone, Yow-Ling Shiue, Chien-Feng Li
PublisherNSYSU
Source SetsNSYSU Electronic Thesis and Dissertation Archive
LanguageCholon
Detected LanguageEnglish
Typetext
Formatapplication/pdf
Sourcehttp://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0810112-224956
Rightsuser_define, Copyright information available at source archive

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