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National Institute of Environmental Health Sciences

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Publication Detail

Title: Enhanced resistance to tamoxifen by the c-ABL proto-oncogene in breast cancer.

Authors: Zhao, Huajun; Ou-Yang, Fu; Chen, I-Fen; Hou, Ming-Feng; Yuan, Shyng-Shiou F; Chang, Hsueh-Ling; Lee, Yi-Chen; Plattner, Rina; Waltz, Susan E; Ho, Shuk-Mei; Sims, Jonathan; Wang, Shao-Chun

Published In Neoplasia, (2010 Mar)

Abstract: 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 a more thorough understanding of how estrogen 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.

PubMed ID: 20234815 Exiting the NIEHS site

MeSH Terms: Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal/therapeutic use*; Breast Neoplasms/drug therapy*; Breast Neoplasms/genetics; Breast Neoplasms/pathology; Carcinoma, Ductal, Breast/drug therapy; Carcinoma, Ductal, Breast/genetics; Carcinoma, Ductal, Breast/pathology; Carcinoma, Intraductal, Noninfiltrating/drug therapy; Carcinoma, Intraductal, Noninfiltrating/genetics; Carcinoma, Intraductal, Noninfiltrating/pathology; Carcinoma, Lobular/drug therapy; Carcinoma, Lobular/genetics; Carcinoma, Lobular/pathology; Cell Line, Tumor; Drug Resistance, Neoplasm*; Estrogen Receptor alpha/genetics; Estrogen Receptor alpha/metabolism*; Female; Gene Expression Regulation, Neoplastic; Gene Silencing; Genes, abl/physiology*; Humans; Middle Aged; RNA, Small Interfering/pharmacology; Receptors, Progesterone/genetics; Receptors, Progesterone/metabolism; Signal Transduction; Tamoxifen/therapeutic use*; Tissue Array Analysis

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Last Reviewed: October 02, 2024