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Identification of Caveolin-1 as a Potential Causative Factor in the Generation of Trastuzumab Resistance in Breast Cancer Cells
The oncogenic tyrosine kinase receptor ErbB2 is a prognostic factor and target for breast cancer therapeutics. In contrast with the other ErbB receptors, ErbB2 is hardly internalized by ligand induced mechanisms, indicating a prevalent surface expression. Elevated levels of ErbB2 in tumor cells are...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3701809/ https://www.ncbi.nlm.nih.gov/pubmed/23833684 http://dx.doi.org/10.7150/jca.6470 |
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author | Sekhar, Sreeja C Kasai, Tomonari Satoh, Ayano Shigehiro, Tsukasa Mizutani, Akifumi Murakami, Hiroshi El-Aarag, Bishoy YA Salomon, David S. Massaguer, Anna de Llorens, Rafael Seno, Masaharu |
author_facet | Sekhar, Sreeja C Kasai, Tomonari Satoh, Ayano Shigehiro, Tsukasa Mizutani, Akifumi Murakami, Hiroshi El-Aarag, Bishoy YA Salomon, David S. Massaguer, Anna de Llorens, Rafael Seno, Masaharu |
author_sort | Sekhar, Sreeja C |
collection | PubMed |
description | The oncogenic tyrosine kinase receptor ErbB2 is a prognostic factor and target for breast cancer therapeutics. In contrast with the other ErbB receptors, ErbB2 is hardly internalized by ligand induced mechanisms, indicating a prevalent surface expression. Elevated levels of ErbB2 in tumor cells are associated with its defective endocytosis and down regulation. Here we show that caveolin-1 expression in breast cancer derived SKBR-3 cells (SKBR-3/Cav-1) facilitates ligand induced ErbB2 endocytosis using an artificial peptide ligand EC-eGFP. Similarly, stimulation with humanized anti ErbB2 antibody Trastuzumab (Herceptin) was found to be internalized and co-localized with caveolin-1 in SKBR-3/Cav-1 cells. Internalized EC-eGFP and Trastuzumab in SKBR-3/Cav-1 cells were then delivered via caveolae to the caveolin-1 containing early endosomes. Consequently, attenuated Fc receptor mediated ADCC functions were observed when exposed to Trastuzumab and EC-Fc (EC-1 peptide conjugated to Fc part of human IgG). On the other hand, this caveolae dependent endocytic synergy was not observed in parental SKBR-3 cells. Therefore, caveolin-1 expression in breast cancer cells could be a predictive factor to estimate how cancer cells are likely to respond to Trastuzumab treatment. |
format | Online Article Text |
id | pubmed-3701809 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-37018092013-07-05 Identification of Caveolin-1 as a Potential Causative Factor in the Generation of Trastuzumab Resistance in Breast Cancer Cells Sekhar, Sreeja C Kasai, Tomonari Satoh, Ayano Shigehiro, Tsukasa Mizutani, Akifumi Murakami, Hiroshi El-Aarag, Bishoy YA Salomon, David S. Massaguer, Anna de Llorens, Rafael Seno, Masaharu J Cancer Research Paper The oncogenic tyrosine kinase receptor ErbB2 is a prognostic factor and target for breast cancer therapeutics. In contrast with the other ErbB receptors, ErbB2 is hardly internalized by ligand induced mechanisms, indicating a prevalent surface expression. Elevated levels of ErbB2 in tumor cells are associated with its defective endocytosis and down regulation. Here we show that caveolin-1 expression in breast cancer derived SKBR-3 cells (SKBR-3/Cav-1) facilitates ligand induced ErbB2 endocytosis using an artificial peptide ligand EC-eGFP. Similarly, stimulation with humanized anti ErbB2 antibody Trastuzumab (Herceptin) was found to be internalized and co-localized with caveolin-1 in SKBR-3/Cav-1 cells. Internalized EC-eGFP and Trastuzumab in SKBR-3/Cav-1 cells were then delivered via caveolae to the caveolin-1 containing early endosomes. Consequently, attenuated Fc receptor mediated ADCC functions were observed when exposed to Trastuzumab and EC-Fc (EC-1 peptide conjugated to Fc part of human IgG). On the other hand, this caveolae dependent endocytic synergy was not observed in parental SKBR-3 cells. Therefore, caveolin-1 expression in breast cancer cells could be a predictive factor to estimate how cancer cells are likely to respond to Trastuzumab treatment. Ivyspring International Publisher 2013-06-21 /pmc/articles/PMC3701809/ /pubmed/23833684 http://dx.doi.org/10.7150/jca.6470 Text en © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. |
spellingShingle | Research Paper Sekhar, Sreeja C Kasai, Tomonari Satoh, Ayano Shigehiro, Tsukasa Mizutani, Akifumi Murakami, Hiroshi El-Aarag, Bishoy YA Salomon, David S. Massaguer, Anna de Llorens, Rafael Seno, Masaharu Identification of Caveolin-1 as a Potential Causative Factor in the Generation of Trastuzumab Resistance in Breast Cancer Cells |
title | Identification of Caveolin-1 as a Potential Causative Factor in the Generation of Trastuzumab Resistance in Breast Cancer Cells |
title_full | Identification of Caveolin-1 as a Potential Causative Factor in the Generation of Trastuzumab Resistance in Breast Cancer Cells |
title_fullStr | Identification of Caveolin-1 as a Potential Causative Factor in the Generation of Trastuzumab Resistance in Breast Cancer Cells |
title_full_unstemmed | Identification of Caveolin-1 as a Potential Causative Factor in the Generation of Trastuzumab Resistance in Breast Cancer Cells |
title_short | Identification of Caveolin-1 as a Potential Causative Factor in the Generation of Trastuzumab Resistance in Breast Cancer Cells |
title_sort | identification of caveolin-1 as a potential causative factor in the generation of trastuzumab resistance in breast cancer cells |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3701809/ https://www.ncbi.nlm.nih.gov/pubmed/23833684 http://dx.doi.org/10.7150/jca.6470 |
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