Enhanced Resistance to Tamoxifen by the c-ABL Proto-oncogene in Breast Cancer
Autor: | Huajun Zhao, Fu Ou-Yang, I-Fen Chen, Ming-Feng Hou, Shyng-Shiou F. Yuan, Hsueh-Ling Chang, Yi-Chen Lee, Rina Plattner, Susan E. Waltz, Shuk-Mei Ho, Jonathan Sims, Shao-Chun Wang |
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Jazyk: | angličtina |
Rok vydání: | 2010 |
Předmět: | |
Zdroj: | Neoplasia: An International Journal for Oncology Research, Vol 12, Iss 3, Pp 214-223 (2010) |
Druh dokumentu: | article |
ISSN: | 1476-5586 1522-8002 |
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: | Directory of Open Access Journals |
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