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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2015.1
- 수록면
- 101 - 109 (9page)
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Purpose Overexpression of cyclooxygenase 2 (COX-2) is thought to promote survival of transformed cells. Transforming growth factor β (TGF-β) exerts anti-proliferative effects on a broad range of epithelial cells. In the current study, we investigated whether TGF-β can regulate COX-2 expression in A549 human lung adenocarcinoma cells, which are TGF-β-responsive and overexpress COX-2. Materials and Methods Western blotting, Northern blotting, and mRNA stability assays were performed to demonstrate that COX-2 protein and mRNA expression were suppressed by TGF-β. We also evaluated the effects of tristetraprolin (TTP) on COX-2 mRNA using RNA interference. Results We demonstrated that COX-2 mRNA and protein expression were both significantly suppressed by TGF-β. An actinomycin D chase experiment demonstrated that COX-2 mRNA was more rapidly degraded in the presence of TGF-β, suggesting that TGF-β-induced inhibition of COX-2 expression is achieved via decreased mRNA stability. We also found that TGF-β rapidly and transiently induced the expression of TTP, a well-known mRNA destabilizing factor, before suppression of COX-2 mRNA expression was observed. Using RNA interference, we confirmed that increased TTP levels play a pivotal role in the destabilization of COX-2 mRNA by TGF-β. Furthermore, we showed that Smad3 is essential to TTP-dependent down-regulation of COX-2 expression in response to TGF-β. Conclusion The results of this study show that TGF-β down-regulated COX-2 expression via mRNA destabilization mediated by Smad3/TTP in A549 cells.
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참고문헌 (23)
참고문헌 신청
Carballo E / 1998 / Feedback inhibition of macrophage tumor necrosis factor-alpha production by tristetraprolin / Science 281 : 1001 ~ 1005
Cha HJ / 2011 / Tristetraprolin downregulates the expression of both VEGF and COX-2 in human colon cancer / Hepatogastroenterology 58 : 790 ~ 795
Chen CY / 2001 / AU binding proteins recruit the exosome to degrade ARE-containing mRNAs / Cell 107 : 451 ~ 464
Dubois RN / 1998 / Cyclooxygenase in biology and disease / FASEB J 12 : 1063 ~ 1073
Gupta RA / 2001 / Colorectal cancer prevention and treatment by inhibition of cyclooxygenase-2 / Nat Rev Cancer 1 : 11 ~ 21
Cha HJ / 2011 / Tristetraprolin downregulates the expression of both VEGF and COX-2 in human colon cancer / Hepatogastroenterology 58 : 790 ~ 795
Chen CY / 2001 / AU binding proteins recruit the exosome to degrade ARE-containing mRNAs / Cell 107 : 451 ~ 464
Dubois RN / 1998 / Cyclooxygenase in biology and disease / FASEB J 12 : 1063 ~ 1073
Gupta RA / 2001 / Colorectal cancer prevention and treatment by inhibition of cyclooxygenase-2 / Nat Rev Cancer 1 : 11 ~ 21
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