@article { author = {Soltantoyeh, Tahereh and Bahadori, Tannaz and Hosseini-Ghatar, Reza and Khoshnoodi, Jalal and Roohi, Azam and Mobini, Maryam and Golsaz-Shirazi, Forough and Jeddi-Tehrani, Mahmood and Amiri, Mohammad Mehdi and Shokri, Fazel}, title = {Differential Effects of Inhibitory and Stimulatory Anti-HER2 Monoclonal Antibodies on AKT/ERK Signaling Pathways}, journal = {Asian Pacific Journal of Cancer Prevention}, volume = {19}, number = {8}, pages = {2255-2262}, year = {2018}, publisher = {West Asia Organization for Cancer Prevention (WAOCP), APOCP's West Asia Chapter.}, issn = {1513-7368}, eissn = {2476-762X}, doi = {10.22034/APJCP.2018.19.8.2255}, abstract = {Objective: Homo- and heterodimerization of the receptor tyrosine kinase HER2 hyperactivate several downstreamsignaling pathways, leading to uncontrolled growth and proliferation of tumor cells. Anti-HER2 monoclonal antibodies(mAbs) may induce different effects on HER2 dimerization and signaling. Methods: The effect of two inhibitory(2A8, 1T0) and one stimulatory (1H9) anti-HER2 mAbs either alone or in combination with trastuzumab was investigatedon AKT and ERK signaling pathways and HER2 degradation in a human breast cancer cell line (BT-474) by Westernblotting. Result: While 1H9 mAb had no significant effect on AKT and ERK signaling pathways, 1T0 and 2A8 mAbsinhibited phosphorylation of both pathways. Combination of 1T0 mAb with trastuzumab resulted in significant synergisticinhibition of both pathways and HER2 degradation, much more potently than the combination of trastuzumab andpertuzumab. Conclusion: Our data indicate that anti-HER2 mAbs may induce different signaling pathways dependingon their effect on tumor cell growth and proliferation. The significant inhibition of ERK and AKT phosphorylation by1T0 alone or particularly in combination with trastuzumab suggests its potential therapeutic application for targetedimmunotherapy of HER2 overexpressing malignancies.}, keywords = {breast cancer,extracellular signal-regulated kinase,human epidermal growth factor receptor 2,signaling pathways,protein kinase B}, url = {https://journal.waocp.org/article_66147.html}, eprint = {https://journal.waocp.org/article_66147_85d5ca2473e4322d9f3cf5b15106b348.pdf} }