PinX1 suppresses bladder urothelial carcinoma cell proliferation via the inhibition of telomerase activity and p16-cyclin D1 pathwayReportar como inadecuado




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Molecular Cancer

, 12:148

First Online: 23 November 2013Received: 28 June 2013Accepted: 19 November 2013DOI: 10.1186-1476-4598-12-148

Cite this article as: Liu, JY., Qian, D., He, LR. et al. Mol Cancer 2013 12: 148. doi:10.1186-1476-4598-12-148

Abstract

BackgroundPIN2-TRF1-interacting telomerase inhibitor1 PinX1 was recently suggested as a putative tumor suppressor in several types of human cancer, based on its binding to and inhibition of telomerase. Moreover, loss of PinX1 has been detected in many human malignancies. However, the possible involvement of PinX1 and its clinical-prognostic significance in urothelial carcinoma of the bladder UCB are unclear.

MethodsThe PinX1 expression profile was examined by quantitative real-time polymerase chain reaction qRT-PCR, western blotting, and immunohistochemistry IHC in UCB tissues and adjacent normal urothelial bladder epithelial tissues. PinX1 was overexpressed and silenced in UCB cell lines to determine its role in tumorigenesis, development of UCB, and the possible mechanism.

ResultsPinX1 expression in UCB was significantly down-regulated at both mRNA and protein level as compared with that in normal urothelial bladder epithelial tissues. PinX1 levels were inversely correlated with tumor multiplicity, advanced N classification, high proliferation index Ki-67, and poor survival P < 0.05. Moreover, overexpression of PinX1 in UCB cells significantly inhibited cell proliferation in vitro and in vivo, whereas silencing PinX1 dramatically enhanced cell proliferation. Overexpression of PinX1 resulted in G1-S phase arrest and cell growth-proliferation inhibition, while silencing PinX1 led to acceleration of G1-S transition, and cell growth-proliferation promotion by inhibiting-enhancing telomerase activity and via the p16-cyclin D1 pathway.

ConclusionsThese findings suggest that down-regulation of PinX1 play an important role in the tumorigenesis and development of UCB and that the expression of PinX1 as detected by IHC is an independent molecular marker in patients with UCB.

KeywordsUrothelial carcinoma of bladder Telomerase activity p16-cyclin D1 pathway Prognosis PinX1 AbbreviationsPinX1PIN2-TRF1-interacting telomerase inhibitor1

UCBUrothelial carcinoma of the bladder

qRT-PCRQuantitative real-time polymerase chain reaction

RCRadical cystectomy

TMATissue microarray

IHCImmunohistochemistry

PIPropidium iodide

CDKCyclin-dependent kinase

RBRetinoblastoma.

Electronic supplementary materialThe online version of this article doi:10.1186-1476-4598-12-148 contains supplementary material, which is available to authorized users.

Jian-Ye Liu, Dong Qian, Li-Ru He, Yong-Hong Li contributed equally to this work.

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Autor: Jian-Ye Liu - Dong Qian - Li-Ru He - Yong-Hong Li - Yi-Ji Liao - Shi-Juan Mai - Xiao-Peng Tian - Yan-Hui Liu - Jia-Xing Z

Fuente: https://link.springer.com/







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