| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2000: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1999: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Research Abstract |
We investigated the mechanisms of apoptosis in neuroblastomas by examining the expression profiles of Fas, Fas ligand and caspase 3 in 42 primary tumor tissues. Immunohistochemically, no or weak Fas expression was detected in 25 out of 29 neuroblastomas (86%), whereas high levels of expression of Fas ligand and procaspase 3 were noted in 30 and 29 of 42 tumors, respectively (〜70%). Overexpression of pro-caspase 3, but not Fas ligand, significantly correlated with a younger age and low tumour stage. Western blot analysis of ten neuroblastomas confirmed the lack of Fas expression and strong FasL expression in all samples and fluent procaspase 3 expression in five tumors that, with the exception of one, belonged to the favorable type. These favorable tumors also showed vigorous Asp-Glu-Val-Asp (DEVD) hydrolytic, or caspase 3-like activities, while the unfavorable tumour lacked such activity. Moreover, immunostaining for p17 subunit of caspase 3 heterodimer showed that active caspase 3 was mainly localized in apoptotic tumourcells. Combined together, our results suggest that caspase 3, activated via a Fas-independent pathway, may play important roles in apoptosis, suppression of growth and, in some cases, regression of favorable neuroblastomas.
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