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Journal of Biochemistry Advance Access originally published online on March 3, 2008
Journal of Biochemistry 2008 143(6):793-801; doi:10.1093/jb/mvn032
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© 2008 The Japanese Biochemical Society

Erbin-regulated Sensitivity of MCF-7 Breast Cancer Cells to TRAIL via ErbB2/AKT/NF-{kappa}B Pathway

Ning Liu, Jindan Zhang, Jinchun Zhang, Shilian Liu, Yanxin Liu and Dexian Zheng*

National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005, China

*To whom correspondence should be addressed. Tel: 8610 6529 6409, Fax: 8610 6510 5102, E-mail: zhengdx{at}pumc.edu.cn or zhengdx{at}tom.com

Received December 28, 2007; Accepted February 19, 2008


  Abstract

We have reported that Erbin expression was down-regulated in the Jurkat leukaemia T lymphocytes treated with the recombinant soluble tumour necrosis factor-related apoptosis-inducing ligand (rsTRAIL). Herein, we studied the expression and the regulation of Erbin and its binding partner, ErbB2, in the MCF-7 breast cancer cell line. We showed that the expressions of Erbin and ErbB2 were modulated by PKC{delta} inhibitor, rottlerin, in the TRAIL-resistant MCF-7 cell line. The affinity of Erbin–ErbB2 interaction was reduced by ErbB2 phosphorylation. Inhibiting the expression of Erbin facilitated the sensitivity of the MCF-7 cells to TRAIL via suppressing the ErbB2/AKT/NF-{kappa}B signalling pathway.

Key Words: apoptosis, breast cancer, erbin, ErbB2, rsTRAIL

Abbreviations: rsTRAIL, recombinant soluble tumor necrosis factor-related apoptosis-inducing ligand; LAP, LRR (leucine-rich repeat) and PDZ; TNF, Tumor necrosis factor; NF-{kappa}B, nuclear factor-kappa B; c-FLIP, FLIC (Fas associated death domain-like IL-1β-converting enzyme)-like inhibitory protein; IAP, inhibitor of apoptosis; EGF, epidermal growth factor


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