| Bladder cancer is the most common urological tumor in China, which has chemo orradioresistant properties and greater potential of accelerated regrowth after a therapeutictreatment. So we need to find a new bladder cancer treatment strategies. Cancer stem cellshave been found in varieties of tumors, which provide a new sight into the initiation,progression and treatment for bladder cancer. Cancer stem cells have aberrant self-renewaland differentiation capacities, and can be formed entirely consistent with the parent cellproperties and function of cells, through asymmetrical division and symmetrical division, tomaintain their self-renewal. And the mutations also can be reserved in cancer stem cells due tothe self-renewal. This shows that the self-renewal is one of the important reasons for cancerstem cells gain the tumorigenicity.Self-renewal in stem cells can be regulated by varieties of pathways. Stemness factorsplays an important role in self-renewal, including Oct4, Sox2and Nanog transcription factors,which regulate the balance of cell proliferation and differentiation, maintain theundifferentiated state of stem cells. Nanog is a recently identified key transcription factor,which maintain pluripotency and self-renewal in the undifferentiated embryonic cells.Research data indicating abnormal high expression levels of Nanog in several types of cancerstem cells, which can enhance the proliferation of tumor cells, and is often accompanied bypoor prognosis. This suggests that Nanog can induce tumorigenesis by maintaining the cancerstem cell self-renewal capacity, promote tumor progression. Research found that bladdercancer stem cells also has high self-renewal capacity, and accompanied by increasedexpression of Nanog. Suggesting that Nanog may be involved the self-renewal in bladdercancer stem cells.However, the effect of Nanog in bladder cancer initiation and progression is not clear. To better understand the expression of Nanog gene in bladder cancer, and the role of Nanog maintainthe stemness in bladder cancer stem cells. First, Western Blot and Immunohistochemistry wereperformed to detect the expression of Nanog gene in bladder cancer stem cells and46cases ofepithelial bladder cancer tissues. We detected that, in bladder cancer stem cells and epithelialbladder cancer tissues expressed significant higher level of Nanog, and increased expressionof Nanog in bladder cancer was significantly associated with a high pathological grade. Then,Nanog was over-expressed by lentivirus in T24and5637cells. And base on the cell model,we used plate colony formation assay to evaluate the effects of Nanog over-expression onproliferation in bladder cancer cells, stem cell culture medium to detect the ability of formingstem cell spheres, plate colony formation assay and MTT method to detect thechemo-sensitivity, transplantation NOD/SCID mice model to analyze tumorigenic potential.The result indicated over-expression Nanog can increase colony formation rate, self renewalcapacity， tumorigenic capacity in bladder cancer cells, and the chemo-sensitivity assayshowed exogenous Nanog expression significantly decreased the chemo-sensitivity of bladdercancer cells to cisplatin compared with the control cells.In summary, increased Nanog expression in epithelial bladder cancer tissues, andincreased expression of Nanog in bladder cancer was significantly associated with a highpathological grade. In addition, we used bladder cancer cell line T24and5637, to identifiedthe function of Nanog in bladder cancer cells. We found over-expression Nanog can increaseproliferation rate, self renewal capacity，drug-resistance in vitro and tumorigenic capacity invivo. The information generated from this study provides a solid base for further study ofthe effect of Nanog in bladder cancer initiation and progression and the mechanism ofdrug-resistant phenotype and cancer recurrence. And provide new candidate for therapy inbladder cancer. |
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