Abstract P5-09-11: BP1, a homeoprotein, regulates estrogen receptor alpha and induces estrogen independence
| Autor: | Samuel J. Simmens, Arnold M. Schwartz, Erika Ginsburg, Patricia E. Berg, Saurabh Kirolikar |
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| Rok vydání: | 2013 |
| Předmět: |
Cancer Research
medicine.medical_specialty medicine.drug_class fungi Cancer Estrogen receptor Biology medicine.disease medicine.disease_cause environment and public health Metastasis enzymes and coenzymes (carbohydrates) Breast cancer Endocrinology Oncology Estrogen Internal medicine medicine Cancer research biological phenomena cell phenomena and immunity Carcinogenesis Estrogen receptor alpha Tamoxifen medicine.drug |
| Zdroj: | Cancer Research. 73:P5-09 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | Introduction: BP1 is a member of the homeobox gene family of transcription factors. Our recent studies have shown that BP1 may play a role in breast cancer cell survival, aggressiveness and metastasis. BP1 protein (pBP1) is expressed in 80% of invasive ductal breast tumors. Moreover, 100% of inflammatory breast tumors are BP1 positive. These data led us to define the mechanism of BP1-related tumorigenesis and aggressiveness in breast cancer. Materials and Methods: MCF-7/O1, O2 and O4 cells overexpressing BP1 and control V1 and V2 cells were tested for growth in estrogen free media, malignant potential and invasiveness using cell viability assays, soft agar assays and matrigel assays, respectively. To determine the influence of BP1 overexpression on tumor characteristics, empty vector cells (V1) and overexpressor cells (O2 and O4) were injected into the fat pads of athymic nude mice. Mice were supplemented with estrogen pellets or were unsupplemented. Chromatin immunoprecipitation assays (ChIP) were used to validate the binding of pBP1 to ERa and EP300. The effects of BP1 expression on ERα and EP300 were investigated using immunoblotting and qRT-PCR. Effects of BP1 overexpression on tamoxifen sensitivity were measured using the MTT assay. Results: Cells overexpressing BP1 showed higher viability (p Conclusion: High BP1 levels can lead to estrogen independence in ER positive breast cancer cells and tumors in mice by at least two mechanisms, indirect and direct, and are associated with resistance to tamoxifen. These results suggest that BP1 may be an important therapeutic target in ER positive breast cancer. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-09-11. |
| Databáze: | OpenAIRE |
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