EpCAM Is Overexpressed in Breast Cancer and Is a Potential Target for Breast Cancer Gene Therapy
| Autor: | Yian Chen, Michael Mitas, Mohamed L. Salem, Walid Osta, William E. Gillanders, Yusuf A. Hannun, Kaidi Mikhitarian, David J. Cole |
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| Rok vydání: | 2004 |
| Předmět: |
Oncology
Cancer Research Small interfering RNA medicine.medical_specialty Transcription Genetic Genetic enhancement Breast Neoplasms Biology chemistry.chemical_compound Breast cancer Antigens Neoplasm Cell Movement Cell Line Tumor Internal medicine medicine Humans Gene silencing Neoplasm Invasiveness Gene Silencing RNA Small Interfering Cell adhesion beta Catenin Cell growth Epithelial cell adhesion molecule Genetic Therapy Cadherins Epithelial Cell Adhesion Molecule medicine.disease Metastatic breast cancer Gene Expression Regulation Neoplastic Cytoskeletal Proteins chemistry Lymphatic Metastasis Trans-Activators Cancer research Female Lymph Nodes Cell Adhesion Molecules Cell Division alpha Catenin |
| Zdroj: | Cancer Research. 64:5818-5824 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | EpCAM (epithelial cell adhesion molecule) is a cell surface molecule that is known to be highly expressed in colon and other epithelial carcinomas. EpCAM is involved in cell-to-cell adhesion and has been the target of antibody therapy in several clinical trials. To assess the value of EpCAM as a novel target for breast cancer gene therapy, we performed real-time reverse transcription-PCR to quantify the level of EpCAM mRNA expression in normal breast tissue and primary and metastatic breast cancers. We found that EpCAM is overexpressed 100- to 1000-fold in primary and metastatic breast cancer. Silencing EpCAM gene expression with EpCAM short interfering RNA (siRNA) resulted in a 35–80% decrease in the rate of cell proliferation in four different breast cancer cell lines. EpCAM siRNA treatment decreased cell migration by 91.8% and cell invasion by 96.4% in the breast cancer cell line MDA-MB-231 in vitro. EpCAM siRNA treatment was also associated with an increase in the detergent-insoluble protein fraction of E-cadherin, α-catenin, and β-catenin, consistent with the known biology of EpCAM as a regulator of cell adhesion. Our hypothesis is that modulation of EpCAM expression can affect cell migration, invasion, and proliferation by enhancing E-cadherin-mediated cell-to-cell adhesion. These data provide compelling evidence that EpCAM is a potential novel target for breast cancer gene therapy and offer insights into the mechanisms associated with EpCAM gene silencing. |
| Databáze: | OpenAIRE |
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