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:	Chaido Sirinian, Anastasios D. Papanastasiou, Soren E. Degn, Theodora Frantzi, Christos Aronis, Dimitrios Chaniotis, Thomas Makatsoris, Angelos Koutras, Haralabos P. Kalofonos
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	breast cancer ER-negative EGFR TKIs RANK-c Genetics QH426-470
Acceso en línea:	https://doaj.org/article/30d05a3f504f497184a3252e2af9cfdd
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spelling	oai:doaj.org-article:30d05a3f504f497184a3252e2af9cfdd2021-11-25T17:40:48ZRANK-C Expression Sensitizes ER-Negative, EGFR-Positive Breast Cancer Cells to EGFR-Tyrosine Kinase Inhibitors (TKIs)10.3390/genes121116862073-4425https://doaj.org/article/30d05a3f504f497184a3252e2af9cfdd2021-10-01T00:00:00Zhttps://www.mdpi.com/2073-4425/12/11/1686https://doaj.org/toc/2073-4425Background: 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.Chaido SirinianAnastasios D. PapanastasiouSoren E. DegnTheodora FrantziChristos AronisDimitrios ChaniotisThomas MakatsorisAngelos KoutrasHaralabos P. KalofonosMDPI AGarticlebreast cancerER-negativeEGFRTKIsRANK-cGeneticsQH426-470ENGenes, Vol 12, Iss 1686, p 1686 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	breast cancer ER-negative EGFR TKIs RANK-c Genetics QH426-470
spellingShingle	breast cancer ER-negative EGFR TKIs RANK-c Genetics QH426-470 Chaido Sirinian Anastasios D. Papanastasiou Soren E. Degn Theodora Frantzi Christos Aronis Dimitrios Chaniotis Thomas Makatsoris Angelos Koutras Haralabos P. Kalofonos RANK-C Expression Sensitizes ER-Negative, EGFR-Positive Breast Cancer Cells to EGFR-Tyrosine Kinase Inhibitors (TKIs)
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.
format	article
author	Chaido Sirinian Anastasios D. Papanastasiou Soren E. Degn Theodora Frantzi Christos Aronis Dimitrios Chaniotis Thomas Makatsoris Angelos Koutras Haralabos P. Kalofonos
author_facet	Chaido Sirinian Anastasios D. Papanastasiou Soren E. Degn Theodora Frantzi Christos Aronis Dimitrios Chaniotis Thomas Makatsoris Angelos Koutras Haralabos P. Kalofonos
author_sort	Chaido Sirinian
title	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_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_sort	rank-c expression sensitizes er-negative, egfr-positive breast cancer cells to egfr-tyrosine kinase inhibitors (tkis)
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/30d05a3f504f497184a3252e2af9cfdd
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RANK-C Expression Sensitizes ER-Negative, EGFR-Positive Breast Cancer Cells to EGFR-Tyrosine Kinase Inhibitors (TKIs)

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