In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 2_suppl ( 2016-01-10), p. 429-429
Abstract:
429 Background: It has been reported that centrosome amplification (CA) facilitate to enhance the malignant potential and poor prognosis in bladder cancer. Besides Aurora A kinase drives CA, many studies suggest that inhibition of Aurora A is promising approach to concur invasive bladder cancer. We assess the novel molecule that is potential regulator of CA in bladder cancer. Methods: From 2000 to 2008, 57 bladder cancer patients treated in our hospital were included in this study. We obtained tumor sample by TUR or radical cystectomy with informed consent. We evaluated status of CA by fluorescent immuno-cytochemistry using anti pericentrin antibody. Then we performed array CGH to clarify hyper amplification gene in CA patients. By another approach, we identified candidate micro RNAs targeting Aurora A by miRNA tip array using CA+ or CA- bladder cancer cell lines. We performed pathway analysis to investigate potential target for CA regulated genes by both strategy. Finally, we found GBAS gene as a potential regulator for CA. Then, we assessed the function of GBAS gene by repressing or overexpressing in vitro and the status of GBAS expression by immunohistochemistry in tumor sample. Results: In CA- cell lines, GBAS overexpression increased CA rate compared with mock cells. Contrary, GBAS knock down reduced CA rate in CA+ cells. Also, in WST-1 assay, GBAS knock down repressed CA+ cell proliferation. While, GBAS overexpression facilitated migration and invasion in CA- cells. By western blot analysis, GBAS overexpression increased Aurora A expression, while GBAS suppression decreased that expression. GBAS knock down also repressed p53 expression in J82 cells. In immunohistochemistry, the patients with high GBAS expression were significant worse cancer specific survival compared with those of low expression (p 〈 0.0001). Conclusions: These results suggest that GBAS gene could be a potential regulator of centrosome duplication via Aurora A expression in bladder cancer. Regulation of GBAS is providing pre-clinical proof-of-principle as promising approach for invasive bladder cancer.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2016.34.2_suppl.429
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2016
detail.hit.zdb_id:
2005181-5
