Erbin-regulated sensitivity of MCF-7 breast cancer cells to TRAIL via ErbB2/AKT/NF-kappaB pathway

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 PKCd 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-iB 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-kB, nuclear factor-kappa B; c-FLIP, FLIC (Fas associated death domain-like IL-1b-converting enzyme)-like inhibitory protein; IAP, inhibitor of apoptosis; EGF, epidermal growth factor. Erbin was originally identified as a binding protein t