Abstract 2999: DEC1 and DEC2 crosstalk between circadian rhythm and tumor progression
| Autor: | Fuyuki Sato, Yasuteru Muragaki |
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| Rok vydání: | 2015 |
| Předmět: | |
| Zdroj: | Cancer Research. 75:2999-2999 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | Circadian rhythms are tightly regulated by clock genes. It has been reported that clock genes plays important roles in biological function of normal cells. However, it is not well understood the function of clock genes in tumor cells. We showed that basic helix-loop-helix (bHLH) transcription factors, differentiated embryonic chondrocyte gene 1 (DEC1/BHLHE40/Sharp2/Stra13) and DEC2 (BHLHE41/Sharp1), are clock genes and play important roles in circadian rhythm, cell proliferation, apoptosis, hypoxia response, various stresses and epithelial-to-mesenchymal transition (EMT) in tumor cells. Various stresses, such as exposure to transforming growth factor-beta (TGF-β), hypoxia, cytokines, serum-free, and anti-tumor drugs affect DEC expression. The increased or decreased DEC expression by such stresses is involved in tumor progression. The evidence that DEC2 has circadian expression in implanted mouse sarcoma cells and negatively regulates VEGF expression under hypoxia. DEC1 has pro-apoptotic effects in human breast cancer cells, whereas DEC2 has anti-apoptotic effects. DEC1 induced EMT by TGF-β in human pancreatic cancer cells, whereas DEC2 suppressed EMT. Immunohistochemical analysis showed that DEC1 is highly expressed in tumor cells and the expression is involved in malignancy. On the other hand, DEC2 is little expressed in tumor cells compared with adjacent non-tumor cells. These findings suggest that DEC1 and DEC2 have different roles in tumor progression under circadian rhythm. DEC2 regulates the circadian rhythm and VEGF expression by negative feed-back system, and DEC1 and DEC2 regulates EMT by positive and negative feed-back system in tumor cells. So, DEC acts as “accelerator” and “brake” in tumor progression. In this study, we show current progress of the DEC genes in tumor progression. Citation Format: Fuyuki Sato, Yasuteru Muragaki. DEC1 and DEC2 crosstalk between circadian rhythm and tumor progression. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2999. doi:10.1158/1538-7445.AM2015-2999 |
| Databáze: | OpenAIRE |
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