Never-in mitosis A-related protein kinase, Nek1, and renal cell c | 560
Translational Medicine

Translational Medicine
Open Access

ISSN: 2161-1025

+44 1223 790975

Never-in mitosis A-related protein kinase, Nek1, and renal cell carcinoma

International Conference on Translational Medicine

September 17-19, 2012 Holiday Inn San Antonio, Texas, USA

Yumay Chen

Scientific Tracks Abstracts: Transl Med

Abstract :

Renal cell carcinoma (RCC) is a heterogeneous disease with poor prognosis because its high resistance to systematic chemotherapy. Overexpression of multiple drug resistance (MDR) has been implicated as one of the mechanisms for RCC�s chemoresistance. Through examination of the expression level of a panel of proteins involved in the DNA damage repair pathway, Never-in mitosis A-related protein kinase 1 (Nek1) was found highly expressed in RCC tumor and cultured RCC cells compared to normal renal tubular epithelial (RTE) cells. Previously, we have shown that association between Nek1 and the voltage dependent anion channel (VDAC1) is tightly regulated and crucial for cell survival in response to genotoxic treatment. Here, we found that elevated protein level of Nek1 leads to prolonged Nek1/VDAC1 association under genotoxic insult. As a result, persistent VDAC1 phosphorylation was found and resulting in VDAC1 channel closure and prevent cells from apoptosis. Thus, increased Nek1 expression in RCC cells keeps the VDAC1 channel closed and prevents apoptosis under genotoxic insult, and may serve an important mechanism in the chemo-resistant phenotype of RCC. Support the hypothesis, down-regulation of Nek1 expression in RCC cells by using the adenovirus mediated shRNA significantly increases the sensitivity of RCC to DNA damaging treatment when compared to cells treated with control virus which silences expression of firefly luciferase. In this study, we show an alterative mechanism to account for RCC�s chemoresistance, thereby providing an additional prognostic marker as well as a potential therapeutic target for drug development in the treatment of RCC.

Biography :

Yumay Chen has completed her Ph.D. degree from University of Texas Health Science Center at San Antonio in 1997. Her research focus is in deciphering the mechanism of genomic instability. She is the past recipient of Carl W. Gottschalk Research Scholar Award from American Society of Nephrology and Patricia Welder Robinson Young Investigator Award from National Kidney Foundation. Currently, she is an Associate Researcher at University of California, Irvine and serves as editorial member on several Journals.