The effects of trastuzumab on HER2-mediated cell signaling in CHO cells expressing human HER2

BMC Cancer
Hamid MaadiZhixiang Wang

Abstract

Targeted therapy with trastuzumab has become a mainstay for HER2-positive breast cancer without a clear understanding of the mechanism of its action. While many mechanisms have been suggested for the action of trastuzumab, most of them are not substantiated by experimental data. It has been suggested that trastuzumab functions by inhibiting intracellular signaling initiated by HER2, however, the data are very controversial. A major issue is the different cellular background of various breast cancer cells lines used in these studies. Each breast cancer cell line has a unique expression profile of various HER receptors, which could significantly affect the effects of trastuzumab. To overcome this problem, in this research we adopted a cell model that allow us to specifically examine the effects of trastuzumab on a single HER receptor without the influence of other HER receptors. Three CHO cell lines stably expressing only human EGFR (CHO-EGFR), HER2 (CHO-K6), or HER3 (CHO-HER3) were used. Various methods including cytotoxicity assay, immunoblotting, indirect immunofluorescence, cross linking, and antibody-dependent cellular cytotoxicity (ADCC) were employed in this research. We showed that trastuzumab did not bind EGFR and HER3, ...Continue Reading

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Citations

May 10, 2020·Journal of Experimental & Clinical Cancer Research : CR·Hui LiHaihe Wang
Feb 28, 2021·Current Research in Translational Medicine·Danesh HassaniFazel Shokri
Apr 8, 2021·Scientific Reports·Amal ElamirGhaleb A Husseini
Jun 23, 2021·Communications Biology·Jakob C StüberAndreas Plückthun
Jul 3, 2021·Cancers·Ryan W Holloway, Paola A Marignani

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Methods Mentioned

BETA
Assay
fluorescence microscopy
electrophoresis

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