Related Experiment Video
Updated: Jun 19, 2026
Orthotopic Transplantation of Breast Tumors as Preclinical Models for Breast Cancer
Published on: May 18, 2020
Prediction of hormone sensitivity for breast cancers
Yasuo Miyoshi1, Keiko Murase, Masaru Saito
1Division of Breast and Endocrine Surgery, Department of Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan. ymiyoshi@hyo-med.ac.jp
Abstract:
The classic action that leads to transcriptional activation of estrogen response genes mediated through estrogen receptors (ER) and the estrogen complex plays a pivotal role in the development of ER-positive breast cancers. In addition to this pathway, non-classic action and non-genomic action, both estrogen-dependent and estrogen-independent genomic actions have also been found to contribute to ER-positive tumor growth. Although the details of these mechanisms are not well known, participation of the growth factor signaling pathway is likely to be the most significant factor for acquisition of resistance to hormonal therapy. This resistance is mediated not only directly through cell growth promotion by growth factor signaling, but also through enhancement of alternative ER signaling pathways in addition to classic action. The reason why tamoxifen-insensitive ER-positive breast cancers respond to aromatase inhibitors may be explained, at least in part, by the different estrogen-related signaling pathways in which aromatase inhibitors may block estrogen signaling. In this paper we discuss the molecular mechanisms for resistance to hormonal therapy based on an understanding of estrogen signaling pathways.
Insights
Estrogen signaling pathways drive ER-positive breast cancer growth and resistance to hormonal therapies. Understanding these complex genomic and non-genomic actions is key to developing effective treatments.
Area of Science:
- Oncology
- Endocrinology
- Molecular Biology
Background:
- Estrogen receptors (ER) mediate classic transcriptional activation of estrogen response genes, crucial in ER-positive breast cancer development.
- Non-classic, non-genomic, and alternative genomic actions of estrogen also contribute to tumor growth.
- Growth factor signaling pathways are implicated in resistance to hormonal therapies for breast cancer.
Purpose of the Study:
- To elucidate the molecular mechanisms underlying resistance to hormonal therapy in ER-positive breast cancers.
- To explore the role of diverse estrogen signaling pathways in treatment resistance.
Main Methods:
- Review and discussion of molecular mechanisms of estrogen signaling.
- Analysis of genomic and non-genomic estrogen actions.
- Investigation of growth factor signaling pathway involvement.
Main Results:
- Growth factor signaling pathways significantly contribute to resistance by promoting cell growth and enhancing alternative ER signaling.
- Alternative ER signaling pathways, beyond the classic action, play a role in tamoxifen resistance.
- Aromatase inhibitors may be effective in tamoxifen-insensitive cancers by blocking specific estrogen signaling pathways.
Conclusions:
- Understanding complex estrogen signaling pathways is critical for overcoming hormonal therapy resistance in ER-positive breast cancer.
- Growth factor signaling and alternative ER pathways are key targets for improving breast cancer treatment strategies.
