Exploring protein–protein interaction in the study of hormone-dependent cancers

Yasuhiro Miki, Erina Iwabuchi, Katsuhiko Ono, Hironobu Sasano, Kiyoshi Ito

Research output: Contribution to journalReview articlepeer-review

15 Citations (Scopus)


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.

Original languageEnglish
Article number3173
JournalInternational Journal of Molecular Sciences
Issue number10
Publication statusPublished - 2018 Oct 15


  • Bioluminescence resonance energy transfer/förster resonance energy transfer
  • Co-immunoprecipitation
  • Estrogen receptor
  • Immunohistochemistry
  • In situ proximity ligation assay
  • Protein–protein interaction
  • Super-resolution microscopy


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