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RANK-C Expression Sensitizes ER-Negative, EGFR-Positive Breast Cancer Cells to EGFR-Tyrosine Kinase Inhibitors (TKIs)

Background: We have previously shown that overexpression of RANK-c in ER-negative breast cancer cell lines attenuates aggressive properties of cancer cells, partially through a RANK-c/EGFR interaction. EGFR inhibition through TKIs in breast cancer has been tested in triple-negative disease settings...

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Autores principales: Sirinian, Chaido, Papanastasiou, Anastasios D., Degn, Soren E., Frantzi, Theodora, Aronis, Christos, Chaniotis, Dimitrios, Makatsoris, Thomas, Koutras, Angelos, Kalofonos, Haralabos P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8619104/
https://www.ncbi.nlm.nih.gov/pubmed/34828291
http://dx.doi.org/10.3390/genes12111686
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author Sirinian, Chaido
Papanastasiou, Anastasios D.
Degn, Soren E.
Frantzi, Theodora
Aronis, Christos
Chaniotis, Dimitrios
Makatsoris, Thomas
Koutras, Angelos
Kalofonos, Haralabos P.
author_facet Sirinian, Chaido
Papanastasiou, Anastasios D.
Degn, Soren E.
Frantzi, Theodora
Aronis, Christos
Chaniotis, Dimitrios
Makatsoris, Thomas
Koutras, Angelos
Kalofonos, Haralabos P.
author_sort Sirinian, Chaido
collection PubMed
description Background: We have previously shown that overexpression of RANK-c in ER-negative breast cancer cell lines attenuates aggressive properties of cancer cells, partially through a RANK-c/EGFR interaction. EGFR inhibition through TKIs in breast cancer has been tested in triple-negative disease settings with limited clinical benefit for patients. Here we test if expression of RANK-c in ER-negative breast cancer cells in conjunction with treatment with TK inhibitors (erlotinib or gefitinib) can affect survival and colony-forming capacity of cancer cells. Methods: Stably expressing MDA-MB-231-RANK-c and SKBR3-RANK-c cells were employed to test proliferation and colony formation in the presence of TKIs. In addition, Western blot analysis was performed to dissect EGFR related signaling cascades upon TK inhibition in the presence of RANK-c. Results: Interestingly the two RANK-c expressing, ER-negative cells lines presented with a distinct phenotype concerning TKI sensitivity upon treatment. MDA-MB-231-RANK-c cells had a higher sensitivity upon gefitinib treatment, while erlotinib decreased the proliferation rate of SKBR3-RANK-c cells. Further, colony formation assays for MDA-MB-231-RANK-c cells showed a decrease in the number and size of colonies developed in the presence of erlotinib. In addition, RANK-c seems to alter signaling through EGFR after TKI treatment in a cell type-specific manner. Conclusions: Our results indicate that ER-negative breast cancer cells that express RANK-c alter their sensitivity profile against tyrosine kinase inhibitors (erlotinib and gefitinib) in a cell type-specific and culture substrate-dependent manner.
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spelling pubmed-86191042021-11-27 RANK-C Expression Sensitizes ER-Negative, EGFR-Positive Breast Cancer Cells to EGFR-Tyrosine Kinase Inhibitors (TKIs) Sirinian, Chaido Papanastasiou, Anastasios D. Degn, Soren E. Frantzi, Theodora Aronis, Christos Chaniotis, Dimitrios Makatsoris, Thomas Koutras, Angelos Kalofonos, Haralabos P. Genes (Basel) Communication Background: We have previously shown that overexpression of RANK-c in ER-negative breast cancer cell lines attenuates aggressive properties of cancer cells, partially through a RANK-c/EGFR interaction. EGFR inhibition through TKIs in breast cancer has been tested in triple-negative disease settings with limited clinical benefit for patients. Here we test if expression of RANK-c in ER-negative breast cancer cells in conjunction with treatment with TK inhibitors (erlotinib or gefitinib) can affect survival and colony-forming capacity of cancer cells. Methods: Stably expressing MDA-MB-231-RANK-c and SKBR3-RANK-c cells were employed to test proliferation and colony formation in the presence of TKIs. In addition, Western blot analysis was performed to dissect EGFR related signaling cascades upon TK inhibition in the presence of RANK-c. Results: Interestingly the two RANK-c expressing, ER-negative cells lines presented with a distinct phenotype concerning TKI sensitivity upon treatment. MDA-MB-231-RANK-c cells had a higher sensitivity upon gefitinib treatment, while erlotinib decreased the proliferation rate of SKBR3-RANK-c cells. Further, colony formation assays for MDA-MB-231-RANK-c cells showed a decrease in the number and size of colonies developed in the presence of erlotinib. In addition, RANK-c seems to alter signaling through EGFR after TKI treatment in a cell type-specific manner. Conclusions: Our results indicate that ER-negative breast cancer cells that express RANK-c alter their sensitivity profile against tyrosine kinase inhibitors (erlotinib and gefitinib) in a cell type-specific and culture substrate-dependent manner. MDPI 2021-10-23 /pmc/articles/PMC8619104/ /pubmed/34828291 http://dx.doi.org/10.3390/genes12111686 Text en © 2021 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 Communication
Sirinian, Chaido
Papanastasiou, Anastasios D.
Degn, Soren E.
Frantzi, Theodora
Aronis, Christos
Chaniotis, Dimitrios
Makatsoris, Thomas
Koutras, Angelos
Kalofonos, Haralabos P.
RANK-C Expression Sensitizes ER-Negative, EGFR-Positive Breast Cancer Cells to EGFR-Tyrosine Kinase Inhibitors (TKIs)
title RANK-C Expression Sensitizes ER-Negative, EGFR-Positive Breast Cancer Cells to EGFR-Tyrosine Kinase Inhibitors (TKIs)
title_full RANK-C Expression Sensitizes ER-Negative, EGFR-Positive Breast Cancer Cells to EGFR-Tyrosine Kinase Inhibitors (TKIs)
title_fullStr RANK-C Expression Sensitizes ER-Negative, EGFR-Positive Breast Cancer Cells to EGFR-Tyrosine Kinase Inhibitors (TKIs)
title_full_unstemmed RANK-C Expression Sensitizes ER-Negative, EGFR-Positive Breast Cancer Cells to EGFR-Tyrosine Kinase Inhibitors (TKIs)
title_short RANK-C Expression Sensitizes ER-Negative, EGFR-Positive Breast Cancer Cells to EGFR-Tyrosine Kinase Inhibitors (TKIs)
title_sort rank-c expression sensitizes er-negative, egfr-positive breast cancer cells to egfr-tyrosine kinase inhibitors (tkis)
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8619104/
https://www.ncbi.nlm.nih.gov/pubmed/34828291
http://dx.doi.org/10.3390/genes12111686
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