Impaired Delta Np63 Expression is Associated with Poor Tumor Development in Transitional Cell Carcinoma of the Bladder

다국어 초록 (Multilingual Abstract)

The oncogenic isoform of the p63 protein, delta Np63 ( Np63), plays an important

role in the pathogenesis of many epithelial carcinomas, and emerging evidences

suggest that Np63 is a promising drug target. However, the functions of Np63

in transitional cell carcinoma of bladder (TCCB) are poorly defined. In this study, a

Np63 shRNA expression vector was transfected into TCCB cell line 5637 and

cell cycling, cell proliferation and protein expression were assessed by flow cytometry

and 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-dimethyl tetrazolium bromide (MTT) assay,

and immunohistochemistry, respectively. The Np63 shRNA expression vector

was also injected into 5637 cell xenograft tumors in nude mice, and tumor size was

measured, tumor tissue morphology was assessed by immunohistopathology and

transmission electron microscopy. In the in vitro study, Np63 shRNA transfection

caused successful Np63 gene silencing and resulted in significant arrest of cell

cycling and cellular proliferation (p<0.05) as well as cyclin D1 expression. In the

nude mouse xenograft model, Np63 shRNA greatly inhibited tumor growth, induced

tumor cell apoptosis (p<0.05) and resulted in cyclin D1 downregulation. Our

data suggest that Np63 may play an oncogenic role in TCCB progression through

promoting cell survival and proliferation. Intratumoral administration of Np63-specific

shRNA suppressed tumor Np63 expression and cellular proliferation while

promoted tumor cellular apoptosis, and therefore inhibited tumor growth and improved

survival of xenograft-bearing mice, which was not accompanied by significant

signs of systemic toxicity.

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