Estradiol promotes rapid degradation of HER3 in ER-positive breast cancer cell line MCF-7 |
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Authors: | Junko Suga Keiko Izumiyama Nobuyuki Tanaka Shigehira Saji |
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Affiliation: | 1. Department of Medical Oncology, Fukushima Medical University, 1 Hikariga-oka, Fukushima-shi, Fukushima 960-1295, Japan;2. Division of Cancer Biology and Therapeutics, Miyagi Cancer Center Research Institute, 47-1 Nodayama, Medeshima-Shiode, Natori, Miyagi 981-1293, Japan;3. Division of Cancer Immunobiology, Department of Cancer Medical Science, Tohoku University Graduate School of Medicine, 2-1 Seiryo Aobaku, Sendai 980-0875, Japan |
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Abstract: | HER3, a member of the receptor tyrosine kinase super family, is overexpressed in a number of cancers, and is associated with malignant phenotypes. Control of the protein stability of the membrane, as well as nuclear receptors, has been known to be an important process affecting tumor cells; however, their relationships have yet to be elucidated. In this study, we demonstrate that estradiol promotes rapid degradation of HER3 via the proteasome pathway in ER-positive breast cancer, MCF-7. ER prevented HER3 degradation, and knockdown of ER expression by si-RNA promoted rapid degradation of HER3. Breakdown of HER3 and ER were regulated by a ubiquitin ligase Nedd4-1 in the presence of estradiol stimulation. We speculate that estradiol quickly degrades ER, making HER3 accessible by Nedd4-1, and leads to the rapid degradation of HER3. In addition, knockdown of ubiquitin ligase Nedd4-1 enhances estradiol induced cell proliferation. These results indicate that HER3 and Nedd4-1 in ER-positive breast cancers might be an important therapeutic target. |
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Keywords: | HER3 Nedd4-1 Estradiol ER Degradation |
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