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. 2020 Jan 24;9(1):bio047662. doi: 10.1242/bio.047662

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© 2020. Published by The Company of Biologists Ltd

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

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Fig. 2. — Mutant ERBB2 confers a resistance to lapatinib and is related to AKT signaling pathway. (A) Overexpression of ERBB2-MT enhances the lapatinib resistance (at 12.5 and 25 μM in comparison with ERBB-WT, both P<0.001). (B) The inhibition curve of AKT inhibitor perifosine. (C) Perifosine blocked shift up of the ERBB2-MT curve under (versus ERBB2-WT) under lapatinib stress. (D) AKT signaling pathway is associated with the ERBB2-MT mutation triggered resistance. Western blotting results confirmed that both ERBB2 strains had a significant increase in ERBB2 (as well as p-ERBB2) expression. Under lapatinib treatment, p-AKT expression was strongly upregulated in the ERBB2-MT group. Combination of the perifosine suppresses the AKT pathway.