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Human Blood Serum Inhibits Ductal Carcinoma Cells BT474 Growth and Modulates Effect of HER2 Inhibition

Trastuzumab, a HER2-targeted antibody, is widely used for targeted therapy of HER2-positive breast cancer (BC) patients; yet, not all of them respond to this treatment. We investigated here whether trastuzumab activity on the growth of HER2-overexpressing BT474 cells may interfere with human periphe...

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Autores principales: Kamashev, Dmitrii, Shaban, Nina, Suntsova, Maria, Raevskiy, Mikhail, Efimov, Victor, Moisseev, Aleksey, Sorokin, Maxim, Buzdin, Anton
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9405390/
https://www.ncbi.nlm.nih.gov/pubmed/36009461
http://dx.doi.org/10.3390/biomedicines10081914
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author Kamashev, Dmitrii
Shaban, Nina
Suntsova, Maria
Raevskiy, Mikhail
Efimov, Victor
Moisseev, Aleksey
Sorokin, Maxim
Buzdin, Anton
author_facet Kamashev, Dmitrii
Shaban, Nina
Suntsova, Maria
Raevskiy, Mikhail
Efimov, Victor
Moisseev, Aleksey
Sorokin, Maxim
Buzdin, Anton
author_sort Kamashev, Dmitrii
collection PubMed
description Trastuzumab, a HER2-targeted antibody, is widely used for targeted therapy of HER2-positive breast cancer (BC) patients; yet, not all of them respond to this treatment. We investigated here whether trastuzumab activity on the growth of HER2-overexpressing BT474 cells may interfere with human peripheral blood endogenous factors. Among 33 individual BC patient blood samples supplemented to the media, BT474 sensitivity to trastuzumab varied up to 14 times. In the absence of trastuzumab, human peripheral blood serum samples could inhibit growth of BT474, and this effect varied ~10 times for 50 individual samples. In turn, the epidermal growth factor (EGF) suppressed the trastuzumab effect on BT474 cell growth. Trastuzumab treatment increased the proportion of BT474 cells in the G0/G1 phases of cell cycle, while simultaneous addition of EGF decreased it, yet not to the control level. We used RNA sequencing profiling of gene expression to elucidate the molecular mechanisms involved in EGF- and human-sera-mediated attenuation of the trastuzumab effect on BT474 cell growth. Bioinformatic analysis of the molecular profiles suggested that trastuzumab acts similarly to the inhibition of PI3K/Akt/mTOR signaling axis, and the mechanism of EGF suppression of trastuzumab activity may be associated with parallel activation of PKC and transcriptional factors ETV1-ETV5.
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spelling pubmed-94053902022-08-26 Human Blood Serum Inhibits Ductal Carcinoma Cells BT474 Growth and Modulates Effect of HER2 Inhibition Kamashev, Dmitrii Shaban, Nina Suntsova, Maria Raevskiy, Mikhail Efimov, Victor Moisseev, Aleksey Sorokin, Maxim Buzdin, Anton Biomedicines Article Trastuzumab, a HER2-targeted antibody, is widely used for targeted therapy of HER2-positive breast cancer (BC) patients; yet, not all of them respond to this treatment. We investigated here whether trastuzumab activity on the growth of HER2-overexpressing BT474 cells may interfere with human peripheral blood endogenous factors. Among 33 individual BC patient blood samples supplemented to the media, BT474 sensitivity to trastuzumab varied up to 14 times. In the absence of trastuzumab, human peripheral blood serum samples could inhibit growth of BT474, and this effect varied ~10 times for 50 individual samples. In turn, the epidermal growth factor (EGF) suppressed the trastuzumab effect on BT474 cell growth. Trastuzumab treatment increased the proportion of BT474 cells in the G0/G1 phases of cell cycle, while simultaneous addition of EGF decreased it, yet not to the control level. We used RNA sequencing profiling of gene expression to elucidate the molecular mechanisms involved in EGF- and human-sera-mediated attenuation of the trastuzumab effect on BT474 cell growth. Bioinformatic analysis of the molecular profiles suggested that trastuzumab acts similarly to the inhibition of PI3K/Akt/mTOR signaling axis, and the mechanism of EGF suppression of trastuzumab activity may be associated with parallel activation of PKC and transcriptional factors ETV1-ETV5. MDPI 2022-08-08 /pmc/articles/PMC9405390/ /pubmed/36009461 http://dx.doi.org/10.3390/biomedicines10081914 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kamashev, Dmitrii
Shaban, Nina
Suntsova, Maria
Raevskiy, Mikhail
Efimov, Victor
Moisseev, Aleksey
Sorokin, Maxim
Buzdin, Anton
Human Blood Serum Inhibits Ductal Carcinoma Cells BT474 Growth and Modulates Effect of HER2 Inhibition
title Human Blood Serum Inhibits Ductal Carcinoma Cells BT474 Growth and Modulates Effect of HER2 Inhibition
title_full Human Blood Serum Inhibits Ductal Carcinoma Cells BT474 Growth and Modulates Effect of HER2 Inhibition
title_fullStr Human Blood Serum Inhibits Ductal Carcinoma Cells BT474 Growth and Modulates Effect of HER2 Inhibition
title_full_unstemmed Human Blood Serum Inhibits Ductal Carcinoma Cells BT474 Growth and Modulates Effect of HER2 Inhibition
title_short Human Blood Serum Inhibits Ductal Carcinoma Cells BT474 Growth and Modulates Effect of HER2 Inhibition
title_sort human blood serum inhibits ductal carcinoma cells bt474 growth and modulates effect of her2 inhibition
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9405390/
https://www.ncbi.nlm.nih.gov/pubmed/36009461
http://dx.doi.org/10.3390/biomedicines10081914
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