Generation of an anti-EpCAM antibody and epigenetic regulation of EpCAM in colorectal cancer
| Autor: | Han-Chung Wu, Yi Ping Wang, Mei-Ying Liao, Tung-Ying Lu, Mark Yen-Ping Kuo |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Cyclin-Dependent Kinase Inhibitor p21
Male Cancer Research Biology medicine.disease_cause Epigenesis Genetic chemistry.chemical_compound Mice Antigens Neoplasm Cell Line Tumor medicine Animals Humans Cell Proliferation Mice Inbred BALB C Oncogene Cell adhesion molecule Cancer Antibodies Monoclonal Epithelial cell adhesion molecule Cell cycle medicine.disease Epithelial Cell Adhesion Molecule HCT116 Cells Molecular biology Xenograft Model Antitumor Assays Oncology chemistry Tumor progression Cancer cell Cancer research MCF-7 Cells Female Tumor Suppressor Protein p53 Carcinogenesis Colorectal Neoplasms Cell Adhesion Molecules |
| Zdroj: | International journal of oncology. 46(4) |
| ISSN: | 1791-2423 |
| Popis: | We have generated a novel monoclonal antibody (mAb), OCAb9-1, which specifically binds to various types of cancer cell lines, but not to normal cells. According to the results of immunoaffinity chromatography, LC-MS/MS analysis, co-immunoprecipitation, and RNA interference studies, the target protein of OCAb9-1 is the epithelial cell adhesion molecule (EpCAM). EpCAM is a type I transmembrane glycoprotein which is highly expressed in epithelial-transformed neoplasia and tumor-initiating cells (TICs). However, regulation of EpCAM gene expression in tumors and its role in tumorigenesis are not fully understood. In the present study, we show that EpCAM expression is elevated in several cancer cell lines and tumor tissues. Loss-of-function experiments were performed to demonstrate that EpCAM negatively regulates expression of p53 and p21, and promotes tumor cell growth, colony formation, migration and invasion. The median overall survival of tumor-bearing mice treated with OCAb9-1 was significantly higher than that of PBS-treated mice. Moreover, we report that the interplay between SUZ12 and JMJD3 results in dynamic regulation of lysine 27 trimethylation of histone 3 (H3K27me3). Taken together, our findings suggest that the anti-EpCAM mAb may be suitable for use in cancer diagnosis, prognosis, imaging and therapy. Furthermore, EpCAM overexpression in cancer cells is strongly associated with tumor progression, and may be regulated by epigenetic mechanisms. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|