@article{d24b8462f5e84cfdb2c3cb50b7a77e1c,
title = "Lack of p38 MAP kinase activation in TRAIL-resistant cells is not related to the resistance to TRAIL-mediated cell death",
abstract = "Activation of MAP kinases is involved in various cellular processes, including immunoregulation, inflammation, cell growth, cell differentiation, and cell death. To investigate the role of p38 MAP kinase activation in the signaling pathway of TRAIL-mediated apoptosis, we compared TRAIL-mediated MAP kinase activation in TRAIL-susceptible human colon cancer cell line DLD1 and TRAIL-resistant DLD1/TRAIL-R cells. TRAIL-mediated activation of ERK occurred in both cell lines. In contrast, both DLD1 and DLD1/TRAIL-R cells showed no obvious JNK activation after treatment with TRAIL. Interestingly, TRAIL-mediated activation of p38 MAP kinases was observed in DLD1 cells but not in DLD1/TRAIL-R cells. However, activation of p38 MAP kinases was observed in both DLD1 and DLD1/TRAIL-R cells after treatment with anisomycin. Furthermore, inhibiting activated p38 MAP kinases with known inhibitors or with an adenovector expressing dominant negative p38α did not block TRAIL-mediated cell death in DLD1 cells. Moreover, activation of p38 MAP kinases by adenovectors expressing constitutive MKK3 or MKK6 (Ad/MKK3bE or Ad/MKK6bE) did not induce cell death in either DLD1 or DLD1/TRAIL-R cell lines. Our results suggest that activation of p38 MAP kinases does not play a major role in TRAIL-mediated apoptosis in DLD1 cells and that lack of TRAIL-mediated p38 MAP kinase activation may not be the mechanism of TRAIL-resistance in DLD1/TRAIL-R cells.",
keywords = "Apoptosis, Cancer, Resistance, TRAIL, p38 MAP kinases",
author = "Lidong Zhang and Hongbo Zhu and Davis, {John J.} and Dietmar Jacob and Shuhong Wu and Fuminori Teraishi and Angelica Gutierrez and Yibin Wang and Bingliang Fang",
note = "Funding Information: resistanceTRAIL, p38 MAP kinases, apoptosis, cancer, For most cell types, TRAIL induces cell death through apoptosis. Although the detailed mechanisms of the signaling pathway of TRAIL-induced apoptosis are still unclear, some important components and steps in the signaling pathway have already been elucidated. The interaction of TRAIL and its two death receptors, DR4 (TRAIL-R1) and/or DR5 We thank Henry H. Peng in the Keck Vector (TRAIL-R2), is the initial step of TRAIL-induced apoptosis.5,6 The binding of TRAIL to Core for adenovirus propagation and quality control, its receptors leads to trimerization and activation of the death receptors. The activated 4 Landes Bioscience. Do N death receptors recruit and activate an adaptor protein called FADD (Fas-associated death Langford for assistance in proffman for editorial reparing the manuseview, and Carrcirei pAt.. domain), which in turn recruits and activates caspase-8, leading to the formation of the This article represents partial fulfillment of the death-inducing signaling complex (DISC).7,8 Once caspase-8 is activated, it can lead to A.G.requirements for the Ph.D. degree for J.D. and apoptosis either by activating effector caspase-3 and -7, which in turn act on final death This work was supported in part by an NCI substrates,8 or by activating Bid, which induces the accumulation of Bax in mitochondria, grants (RO1 CA 092487-01A1 and RO1 CA the release of cytochrome c from mitochondria, the activation of caspases-9, -3, and -7, and 098582-01A1 to B.F.); a grant from The W.M.{\textcopyright} 200 finally programmed cell death.9,10 Copyright: Copyright 2017 Elsevier B.V., All rights reserved.",
year = "2004",
month = mar,
doi = "10.4161/cbt.3.3.696",
language = "English",
volume = "3",
pages = "296--301",
journal = "Cancer Biology and Therapy",
issn = "1538-4047",
publisher = "Landes Bioscience",
number = "3",
}
