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@article{1203458, author = {Zdražilová Dubská, Lenka and Anděra, Ladislav and Sheard, MA}, article_number = {19}, doi = {http://dx.doi.org/10.1016/j.febslet.2005.06.047}, issn = {0014-5793}, journal = {FEBS Letters}, title = {HER2 signaling downregulation by trastuzumab and suppression of the PI3K/Akt pathway: An unexpected effect on TRAIL-induced apoptosis}, volume = {579}, year = {2005} }
TY - JOUR ID - 1203458 AU - Zdražilová Dubská, Lenka - Anděra, Ladislav - Sheard, MA PY - 2005 TI - HER2 signaling downregulation by trastuzumab and suppression of the PI3K/Akt pathway: An unexpected effect on TRAIL-induced apoptosis JF - FEBS Letters VL - 579 IS - 19 SP - 4149-4158 EP - 4149-4158 PB - North Holland SN - 00145793 N2 - We investigated whether HER2 downregulation by trastuzumab modulates the responsiveness of breast cancer cells to TNF-related apoptosis-inducing ligand (TRAIL). Interestingly, in contrast to increased response to TRAIL in SKBr3 cells, trastuzumab decreased the susceptibility of BT474 cells to TRAIL. This decrease was also observed after exogenous inhibition of P13-K/Akt kinase, but not MAPK/ERK kinase (MEK)/mitogen-activated protein kinase (MAPK). In BT474 cells, but not SKBr3 cells, inhibition of the HER2/phosphatidylinositol 3' kinase (PI3K)/Akt pathway resulted in downregulation of the pro-apoptotic receptors TRAIL-receptor 1 (TRAIL-R1) and TRAIL-R2. TRAIL-induced caspase-8 activation, Bid processing, drop of AT., and poly ADP-ribose polymerase (PARP) cleavage but not in caspase-9 activation, and these events were inhibited in HER2/PI3K/Akt-suppressed BT474 cells, which on the other hand exhibited downregulation of BCl-X-L and increased response to mitomycin C. We show that HER2/PI3K/Akt pathway may play a specific pro-apoptotic role in certain cell type by inducing TRAIL-R1 and -R2 expression and thereby enhancing responsiveness to TRAIL. (c) 2005 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies. ER -
ZDRAŽILOVÁ DUBSKÁ, Lenka, Ladislav ANDĚRA a MA SHEARD. HER2 signaling downregulation by trastuzumab and suppression of the PI3K/Akt pathway: An unexpected effect on TRAIL-induced apoptosis. \textit{FEBS Letters}. North Holland, 2005, roč.~579, č.~19, s.~4149-4158. ISSN~0014-5793. Dostupné z: https://dx.doi.org/10.1016/j.febslet.2005.06.047.
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