Apoptosis in favourable neuroblastomas is not dependent on Fas (CD95/APO-1) expression but on activated caspase 3 (CPP32)
✍ Scribed by Koizumi, Hirotaka; Ohkawa, Ikuo; Tsukahara, Toshifumi; Momoi, Takashi; Nakada, Koonosuke; Uchikoshi, Toshiyuki
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 352 KB
- Volume
- 189
- Category
- Article
- ISSN
- 0022-3417
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✦ Synopsis
The mechanisms of apoptosis in neuroblastomas have been investigated by examining the expression profiles of Fas, Fas ligand (FasL), and caspase 3 in 42 primary tumour tissues. Immunohistochemically, no or weak Fas expression was detected in 25 out of 29 neuroblastomas (86 per cent), whereas high levels of expression of FasL and pro-caspase 3 were noted in 30 and 29 of 42 tumours, respectively (70 per cent). Overexpression of pro-caspase 3, but not FasL, correlated significantly with a younger age and low tumour stage. Western blot analysis of ten neuroblastomas confirmed the lack of Fas expression and the presence of strong FasL expression in all samples and pro-caspase 3 expression in five tumours, of which four belonged to the favourable type. These favourable tumours also showed vigorous Asp-Glu-Val-Asp (DEVD) hydrolytic, or caspase 3-like activities, while the unfavourable tumour lacked such activity. Moreover, immunostaining for the p17 subunit of the caspase 3 heterodimer showed that active caspase 3 was mainly localized in apoptotic tumour cells. 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 favourable neuroblastomas.