PAX2 Protein Induces Expression of Cyclin D1 through Activating AP-1 Protein and Promotes Proliferation of Colon Cancer Cells
| Autor: | Hai-Sheng Zhang, Yun-Fang Zhang, Xuebing Li, Bing Yan, li（范莉） Fan, Jing（方靖） Fang, Guohao Wu, Min Li |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Male
animal structures Proto-Oncogene Proteins c-jun JUNB Cyclin D Cyclin A Cyclin B Mice Nude urologic and male genital diseases medicine.disease_cause Biochemistry Mice Cyclin D1 Cell Line Tumor medicine Animals Humans Molecular Biology Cell Proliferation Mice Inbred BALB C biology urogenital system PAX2 Transcription Factor c-jun Cell Biology Up-Regulation Transcription Factor AP-1 body regions Colonic Neoplasms embryonic structures biology.protein Cancer research sense organs Carcinogenesis Proto-Oncogene Proteins c-fos Cyclin A2 Signal Transduction |
| Zdroj: | Journal of Biological Chemistry. 287:44164-44172 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m112.401521 |
| Popis: | Paired box (PAX) 2, a transcription factor, plays a critical role in embryogenesis. When aberrantly expressed in adult tissues, it generally exhibits oncogenic properties. However, the underlying mechanisms remain unclear. We reported previously that the expression of PAX2 was up-regulated in human colon cancers. However, the role of PAX2 in colon cancer cells has yet to be determined. The aim of this study is to determine the function of PAX2 in colon cancer cells and to investigate the possible mechanisms underlain. We find that knockdown of PAX2 inhibits proliferation and xenograft growth of colon cancer cells. Inhibition of PAX2 results in a decreased expression of cyclin D1. Expression of cyclin D1 is found increased in human primary colon malignant tumors, and its expression is associated with that of PAX2. These data indicate that PAX2 is a positive regulator of expression of cyclin D1. We find that knockdown of PAX2 inhibits the activity of AP-1, a transcription factor that induces cyclin D1 expression, implying that PAX2 induces cyclin D1 through AP-1. PAX2 has little effect on expression of AP-1 members including c-Jun, c-Fos, and JunB. Our data show that PAX2 prevents JunB from binding c-Jun and enhances phosphorylation of c-Jun, which may elevate the activity of AP-1. Taken together, these results suggest that PAX2 promotes proliferation of colon cancer cells through AP-1. |
| Databáze: | OpenAIRE |
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