Elevated expression of CUEDC2 protein confers endocrine resistance in breast cancer
| Autor: | Bing Liang, Xin Pan, Cheng Zhen, Zhao Jian, Wei-Li Gong, Hui Yan Li, Li Xin Wei, Yan Hong Tai, Jie Zhao, Yuan Chen, Xue-Min Zhang, Jiang Hong Man, Rui Mu, Zhao Fang Bai, Ai-Ling Li, Tao Zhou, Chenguang Wang, Yan Fei Gao, Yuan Cao, Peijing Zhang, Wei-Na Zhang, Ming Yu |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Oncology
medicine.medical_specialty Antineoplastic Agents Hormonal Endocrine resistance Regulator Down-Regulation Estrogen receptor Tamoxifen treatment Breast Neoplasms Biology General Biochemistry Genetics and Molecular Biology Breast cancer Downregulation and upregulation Cell Line Tumor Internal medicine medicine Tamoxifen resistance Humans Phosphorylation skin and connective tissue diseases Adaptor Proteins Signal Transducing Estrogen Receptor alpha Ubiquitination Membrane Proteins General Medicine medicine.disease I-kappa B Kinase Gene Expression Regulation Neoplastic Tamoxifen Drug Resistance Neoplasm Female Carrier Proteins Receptors Progesterone medicine.drug |
| Zdroj: | Nature Medicine. 17:708-714 |
| ISSN: | 1546-170X 1078-8956 |
| DOI: | 10.1038/nm.2369 |
| Popis: | Endocrine resistance is a major obstacle to hormonal therapy for breast cancers. Although reduced expression of estrogen receptor-α (ER-α) is a known contributing factor to endocrine resistance, the mechanism of ER-α downregulation in endocrine resistance is still not fully understood. Here we report that CUE domain-containing protein-2 (CUEDC2), a ubiquitin-binding motif-containing protein, is a key factor in endocrine resistance in breast cancer. We show that CUEDC2 modulates ER-α protein stability through the ubiquitin-proteasome pathway. Through the study of specimens from a large cohort of subjects with breast cancer, we found a strong inverse correlation between CUEDC2 and ER-α protein expression. Notably, subjects with tumors that highly expressed CUEDC2 had poor responsiveness to tamoxifen treatment and high potential for relapse. We further show that ectopic CUEDC2 expression impaired the responsiveness of breast cancer cells to tamoxifen. Therefore, our findings suggest that CUEDC2 is a crucial determinant of resistance to endocrine therapies in breast cancer. |
| Databáze: | OpenAIRE |
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