Kondo Y, Kondo S, Liu J, Haqqi T, Barnett G H, Barna B P
Department of Neurosciences, Cleveland Clinic Foundation, Ohio 44195, USA.
Exp Cell Res. 1997 Oct 10;236(1):51-6. doi: 10.1006/excr.1997.3693.
Retinoblastoma is an intraocular malignancy of childhood, which is very radiosensitive. gamma-irradiation, however, induces side effects, and the precise mechanisms of tumor cell death after the treatment remain unknown. In this study, we demonstrated that gamma-irradiation induced apoptosis (programmed cell death) in human retinoblastoma cell lines Y79 and WERI-Rb-1. The expression levels of p53, tumor suppressor gene product, and its-associated protein, WAF1/CIP1, were both up-regulated, and function of p53 was remarkably activated after the treatment. Moreover, apoptosis was induced in the absence of gamma-irradiation by overexpression of the WAF1/CIP1 gene in both retinoblastoma cells. These results indicate that the transfer of the WAF1/CIP1 gene may have potential for the treatment of human retinoblastomas instead of gamma-irradiation.
视网膜母细胞瘤是一种儿童眼内恶性肿瘤，对放疗非常敏感。然而，γ射线照射会产生副作用，治疗后肿瘤细胞死亡的确切机制仍不清楚。在本研究中，我们证明γ射线照射可诱导人视网膜母细胞瘤细胞系Y79和WERI-Rb-1发生凋亡（程序性细胞死亡）。肿瘤抑制基因产物p53及其相关蛋白WAF1/CIP1的表达水平均上调，且治疗后p53的功能显著激活。此外，在两种视网膜母细胞瘤细胞中，通过过表达WAF1/CIP1基因，在没有γ射线照射的情况下也可诱导凋亡。这些结果表明，WAF1/CIP1基因的转移可能具有替代γ射线照射治疗人类视网膜母细胞瘤的潜力。
