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
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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