초록 ▼

원발성 간암세포에서의 약30%정도에서 β-catenin mutation이 발견되고 있다. 이 결과는 wnt/β-catenin pathway가 간암발생에서 관련이 있음을 시사하고 있다. 본 과제에서는 간암발생에서 wnt/β-catenin pathway의 중요성을 조사하였다. 구체적으로, wnt/β-catenin pathway에 관련된 유전자를 간암세포주에 transfection 한 후 Lef-luciferse reporter assay를 통하여 wnt/β-catenin pathway의 activationm을 조사하였다. 또한, wnt

원발성 간암세포에서의 약30%정도에서 β-catenin mutation이 발견되고 있다. 이 결과는 wnt/β-catenin pathway가 간암발생에서 관련이 있음을 시사하고 있다. 본 과제에서는 간암발생에서 wnt/β-catenin pathway의 중요성을 조사하였다. 구체적으로, wnt/β-catenin pathway에 관련된 유전자를 간암세포주에 transfection 한 후 Lef-luciferse reporter assay를 통하여 wnt/β-catenin pathway의 activationm을 조사하였다. 또한, wnt/β-catenin pathway의 nuclear target인 COX-2 expression을 조사하여 wnt/β-catenin pathway의 relevance를 규명하고자 하였다.

Abstract ▼

Wnt signaling has been described in wing development of Drosophila and colon carcinogenesis. Recently, mutations of β-catenin, a hallmark of Wnt signaling, were reported in significant numbers of primary HCC. However, it is not known whether β-catenin mutation lead to the activation of Wnt signaling

Wnt signaling has been described in wing development of Drosophila and colon carcinogenesis. Recently, mutations of β-catenin, a hallmark of Wnt signaling, were reported in significant numbers of primary HCC. However, it is not known whether β-catenin mutation lead to the activation of Wnt signaling in hepatoma cells. To address this, six hepatoma cell lines were examined for (i) activation of Wnt signaling by reporter assay and (ii) nuclear localization of β-catenin by immunostaining following ectopic expression of Wnt signaling molecules. We found that a Wnt signal, such as Wnt-1, is necessary but not sufficient for the stabilization and subsequent nuclear localization of β-catenin in some hepatoma cells. The data substantiated a notion that Wnt signaling was involved in development of a subset of HCC.
Cycolooxygenase-2 (COX-2) has been suggested to be associated with carcinogenesis. In HCC, the expression pattern of COX-2 protein suggested that abnormal COX-2 expression plays an important role in hepatocarcinogenesis. We investigated the expression pattern and clinical significance of COX-2 in HCC tissues. In addition, we evaluated the efficacy of a selective COX-2 inhibitor, NS-398. Immunohistochemically, all six well-differentiated HCCs were positive, while 83% (10/12) of the poorly differentiated HCCs were negative. All cell lines exhibited appoptosis. In conclusion, COX-2 may be a determinant of the differentiation grade of HCC and the inhibition of COX-2 can induce growth suppression of hepatoma cell lines via induction of apoptosis.

목차 Contents

• 제1장 서론...9
• 제2장 국내외 기술개발 현황...13
• 제3장 연구개발수행 내용 및 결과...14
• 제4장 연구개발목표 달성도 및 대외기여도...34
• 제5장 연구개발결과의 활용계획...35
• 제6장 참고문헌...36