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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
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In inflammation-associated carcinogenesis, COX-2 is markedly overexpressed, resulting in accumulation of various prostaglandins. 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) is one of the terminal products of COX-2-catalyzed arachidonic acid catabolism with oncogenic potential. Epithelial-to-mesenchymal transition (EMT) is a process by which epithelial cells lose their polarity and adhesiveness, and thereby gain migratory and invasive properties. Treatment of human breast cancer MCF-7 cells with 15d-PGJ2 induced EMT as evidenced by increased expression of Snail and ZEB1, with concurrent down-regulation of E-cadherin. Nuclear extract from 15d-PGJ2-treated MCF-7 cells showed the binding of Snail and ZEB1 to E-box sequences present in the E-cadherin promoter, which accounts for repression of E-catherin expression. Unlike 15d-PGJ2, its non-electrophilic analogue 9,10-dihydro- 15d-PGJ2 failed to induce EMT, suggesting that the α,β-unsaturated carbonyl group located in the cyclopentenone ring of 15d-PGJ2 is essential for its oncogenic function. Notably, the mRNA level of interleukin-8 (IL-8)/CXCL8 was highly elevated in 15d-PGJ2-stimulated MCF-7 cells. 15d-PGJ2-induced up-regulation of IL-8/CXCL8 expression was abrogated by silencing of Snail short interfering RNA. Treatment of normal fibroblast with conditioned medium obtained from cultures of MCF-7 cells undergoing EMT induced the expression of activated fibroblast marker proteins, α-smooth muscle actin and fibroblasts activation protein-α. Co-culture of normal fibroblasts with 15d-PGJ2-stimulated MCF-7 cells also activated normal fibroblast cells to cancer associated fibroblasts. Taken together, above findings suggest that 15d-PGJ2 induces EMT through up-regulation of Snail expression and subsequent production of CXCL8 as a putative activator of fibroblasts, which may contribute to tumor-stroma interaction in inflammatory breast cancer microenvironment.
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참고문헌 (32)
참고문헌 신청
Sporn MB / 1996 / The war on cancer / Lancet 347:1377~1381
Kalluri R / 2009 / EMT : when epithelial cells decide to become mesenchymal-like cells / J Clin Invest 119:1417~1419
Maeda M / 2005 / Cadherin switching : essential for behavioral but not morphological changes during an epithelium-to-mesenchyme transition / J Cell Sci 118(Pt 5):873~887
Schulte J / 2012 / Expression of the E-cadherin repressors Snail, Slug and Zeb1in urothelial carcinoma of the urinary bladder : relation to stromal fibroblast activation and invasive behaviour of carcinoma cells / Histochem Cell Biol 138:847~860
Mantovani A / 2008 / Cancer-related inflammation / Nature 454:436~444
Kalluri R / 2009 / EMT : when epithelial cells decide to become mesenchymal-like cells / J Clin Invest 119:1417~1419
Maeda M / 2005 / Cadherin switching : essential for behavioral but not morphological changes during an epithelium-to-mesenchyme transition / J Cell Sci 118(Pt 5):873~887
Schulte J / 2012 / Expression of the E-cadherin repressors Snail, Slug and Zeb1in urothelial carcinoma of the urinary bladder : relation to stromal fibroblast activation and invasive behaviour of carcinoma cells / Histochem Cell Biol 138:847~860
Mantovani A / 2008 / Cancer-related inflammation / Nature 454:436~444
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