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Exploring Protein–Protein Interaction in the Study of Hormone-Dependent Cancers

Estrogen receptors promote target gene transcription when they form a dimer, in which two identical (homodimer) or different (heterodimer) proteins are bound to each other. In hormone-dependent cancers, hormone receptor dimerization plays pivotal roles, not only in the pathogenesis or development of...

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Autores principales: Miki, Yasuhiro, Iwabuchi, Erina, Ono, Katsuhiko, Sasano, Hironobu, Ito, Kiyoshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6213999/
https://www.ncbi.nlm.nih.gov/pubmed/30326622
http://dx.doi.org/10.3390/ijms19103173
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author Miki, Yasuhiro
Iwabuchi, Erina
Ono, Katsuhiko
Sasano, Hironobu
Ito, Kiyoshi
author_facet Miki, Yasuhiro
Iwabuchi, Erina
Ono, Katsuhiko
Sasano, Hironobu
Ito, Kiyoshi
author_sort Miki, Yasuhiro
collection PubMed
description Estrogen receptors promote target gene transcription when they form a dimer, in which two identical (homodimer) or different (heterodimer) proteins are bound to each other. In hormone-dependent cancers, hormone receptor dimerization plays pivotal roles, not only in the pathogenesis or development of the tumors, but also in the development of therapeutic resistance. Protein–protein interactions (PPIs), including dimerization and complex formation, have been also well-known to be required for proteins to exert their functions. The methods which could detect PPIs are genetic engineering (i.e., resonance energy transfer) and/or antibody technology (i.e., co-immunoprecipitation) using cultured cells. In addition, visualization of the target proteins in tissues can be performed using antigen–antibody reactions, as in immunohistochemistry. Furthermore, development of microscopic techniques (i.e., electron microscopy and confocal laser microscopy) has made it possible to visualize intracellular and/or intranuclear organelles. We have recently reported the visualization of estrogen receptor dimers in breast cancer tissues by using the in situ proximity ligation assay (PLA). PLA was developed along the lines of antibody technology development, and this assay has made it possible to visualize PPIs in archival tissue specimens. Localization of PPI in organelles has also become possible using super-resolution microscopes exceeding the resolution limit of conventional microscopes. Therefore, in this review, we summarize the methodologies used for studying PPIs in both cells and tissues, and review the recently reported studies on PPIs of hormones.
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spelling pubmed-62139992018-11-14 Exploring Protein–Protein Interaction in the Study of Hormone-Dependent Cancers Miki, Yasuhiro Iwabuchi, Erina Ono, Katsuhiko Sasano, Hironobu Ito, Kiyoshi Int J Mol Sci Review Estrogen receptors promote target gene transcription when they form a dimer, in which two identical (homodimer) or different (heterodimer) proteins are bound to each other. In hormone-dependent cancers, hormone receptor dimerization plays pivotal roles, not only in the pathogenesis or development of the tumors, but also in the development of therapeutic resistance. Protein–protein interactions (PPIs), including dimerization and complex formation, have been also well-known to be required for proteins to exert their functions. The methods which could detect PPIs are genetic engineering (i.e., resonance energy transfer) and/or antibody technology (i.e., co-immunoprecipitation) using cultured cells. In addition, visualization of the target proteins in tissues can be performed using antigen–antibody reactions, as in immunohistochemistry. Furthermore, development of microscopic techniques (i.e., electron microscopy and confocal laser microscopy) has made it possible to visualize intracellular and/or intranuclear organelles. We have recently reported the visualization of estrogen receptor dimers in breast cancer tissues by using the in situ proximity ligation assay (PLA). PLA was developed along the lines of antibody technology development, and this assay has made it possible to visualize PPIs in archival tissue specimens. Localization of PPI in organelles has also become possible using super-resolution microscopes exceeding the resolution limit of conventional microscopes. Therefore, in this review, we summarize the methodologies used for studying PPIs in both cells and tissues, and review the recently reported studies on PPIs of hormones. MDPI 2018-10-15 /pmc/articles/PMC6213999/ /pubmed/30326622 http://dx.doi.org/10.3390/ijms19103173 Text en © 2018 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Miki, Yasuhiro
Iwabuchi, Erina
Ono, Katsuhiko
Sasano, Hironobu
Ito, Kiyoshi
Exploring Protein–Protein Interaction in the Study of Hormone-Dependent Cancers
title Exploring Protein–Protein Interaction in the Study of Hormone-Dependent Cancers
title_full Exploring Protein–Protein Interaction in the Study of Hormone-Dependent Cancers
title_fullStr Exploring Protein–Protein Interaction in the Study of Hormone-Dependent Cancers
title_full_unstemmed Exploring Protein–Protein Interaction in the Study of Hormone-Dependent Cancers
title_short Exploring Protein–Protein Interaction in the Study of Hormone-Dependent Cancers
title_sort exploring protein–protein interaction in the study of hormone-dependent cancers
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6213999/
https://www.ncbi.nlm.nih.gov/pubmed/30326622
http://dx.doi.org/10.3390/ijms19103173
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