caa a22 4500 605491895 CHVBK 20210128100512.0 cr unu---uuuuu 210128e20150401xx s 000 0 eng 10.1007/s10147-015-0788-5 doi (NATIONALLICENCE)springer-10.1007/s10147-015-0788-5 Mechanisms of hormonal therapy resistance in breast cancer [Elektronische Daten] [Shin-ichi Hayashi, Mariko Kimura] Abstract : Whilst estrogen receptor (ER)-positive breast cancers are preferentially treated with hormone therapy, approximately one-third of them relapse. The mechanisms of refractoriness have been investigated by numerous studies but have not been fully clarified. Hormonal therapy resistance, particularly aromatase inhibitor (AI) resistance, may be related to the acquisition of alternative intracellular ER signaling. We have been investing the mechanisms using cancer specimens and cell lines by monitoring the transcription activity of ERs. AI refractory specimens showed diverse ER activity in the adenovirus estrogen receptor element-green fluorescent protein (ERE-GFP) assay and varied sensitivity to anti-estrogens, indicating the existence of multiple resistant mechanisms. We established six different types of cell lines mimicking AI resistance from ERE-GFP-introduced ER-positive cell lines. They revealed that multiple and alternative ER activating pathways were involved in the resistance, such as phosphorylation-dependent or androgen metabolite-dependent mechanisms. The response to fulvestrant and mammalian target of rapamycin inhibitor also varied among individual resistant cell lines. These results indicate that further subclassification of ER-positive breast cancer is extremely important to decide the therapeutic management of not only hormonal therapy but also new molecular target therapy. Japan Society of Clinical Oncology, 2015 Estrogen receptor nationallicence Aromatase inhibitor nationallicence Hormonal therapy nationallicence Androgen nationallicence mTOR nationallicence Hayashi Shin-ichi Department of Molecular and Functional Dynamics, and Center for Regulatory Epigenomics and Diseases, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Japan aut Kimura Mariko Department of Molecular and Functional Dynamics, and Center for Regulatory Epigenomics and Diseases, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Japan aut International Journal of Clinical Oncology Springer Japan 20/2(2015-04-01), 262-267 1341-9625 20:2<262 2015 20 10147 https://doi.org/10.1007/s10147-015-0788-5 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 review-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s10147-015-0788-5 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Hayashi Shin-ichi Department of Molecular and Functional Dynamics, and Center for Regulatory Epigenomics and Diseases, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Japan aut NATIONALLICENCE 700 1- Kimura Mariko Department of Molecular and Functional Dynamics, and Center for Regulatory Epigenomics and Diseases, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Japan aut NATIONALLICENCE 773 0- International Journal of Clinical Oncology Springer Japan 20/2(2015-04-01), 262-267 1341-9625 20:2<262 2015 20 10147