Enhanced Resistance to Tamoxifen by the c-ABL Proto-oncogene in Breast Cancer
Autor: | Jonathan T. Sims, Shyng-Shiou F. Yuan, Susan E. Waltz, Hsueh-Ling Chang, Yi-Chen Lee, Huajun Zhao, Ming-Feng Hou, Rina Plattner, I-Fen Chen, Fu Ou-Yang, Shao Chun Wang, Shuk-Mei Ho |
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Jazyk: | angličtina |
Předmět: |
Cancer Research
Estrogen receptor Proto-Oncogene Mas Estrogen-related receptor alpha 0302 clinical medicine hemic and lymphatic diseases RNA Small Interfering skin and connective tissue diseases Aged 80 and over 0303 health sciences Carcinoma Ductal Breast Middle Aged lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens 3. Good health Gene Expression Regulation Neoplastic 030220 oncology & carcinogenesis Female Receptors Progesterone hormones hormone substitutes and hormone antagonists medicine.drug Signal Transduction Research Article Adult Antineoplastic Agents Hormonal medicine.drug_class Breast Neoplasms Biology Genes abl lcsh:RC254-282 03 medical and health sciences Breast cancer Cell Line Tumor medicine Humans Gene Silencing Estrogen receptor beta 030304 developmental biology Aged Estrogen Receptor alpha Cancer medicine.disease Carcinoma Lobular Tamoxifen Carcinoma Intraductal Noninfiltrating Estrogen Drug Resistance Neoplasm Tissue Array Analysis Cancer research Estrogen receptor alpha |
Zdroj: | Neoplasia: An International Journal for Oncology Research, Vol 12, Iss 3, Pp 214-223 (2010) |
ISSN: | 1476-5586 |
DOI: | 10.1593/neo.91576 |
Popis: | Targeting the estrogen receptor is an important strategy in breast cancer therapy. However, although inhibiting estrogen receptor function with specific estrogen receptor modulators can achieve a primary response in cancer patients, intrinsic or subsequently acquired resistance to the therapy remains a major obstacle in the clinic. Thus, it is critical to gain amore thorough understanding of howestrogen receptor functions are regulated in breast cancer.Here, we demonstrate that the non-receptor tyrosine kinase c-ABL is a functional partner of the estrogen receptor, as expression of c-ABL sustained transcriptional activity of the estrogen receptor. More importantly, inhibition of c-ABL resulted in sensitization to treatment by tamoxifen (TAM) in estrogen receptor-positive breast cancer cells, as manifested by inhibition of cell survival and suppression of anchorage-independent growth. We found that c-ABL interacts with estrogen receptor in breast cancer cells and that expression of c-ABL is a frequent event in primary breast cancer tumor tissues. In estrogen receptor-positive tumors, the expression of c-ABL significantly correlated with disease progression and metastasis. This study shows that c-ABL regulates the cellular response to TAM through functional interaction with the estrogen receptor, which suggests c-ABL as a therapeutic target and a prognostic tumor marker for breast cancer. |
Databáze: | OpenAIRE |
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