转录激活缺陷型DeltaTA-p73作为一种癌基因发挥作用。

Transactivation-deficient DeltaTA-p73 acts as an oncogene.

作者信息

Stiewe Thorsten, Zimmermann Sonja, Frilling Andreja, Esche Helmut, Pützer Brigitte M

机构信息

Centre for Cancer Research and Cancer Therapy, Institute of Molecular Biology, University of Essen, Medical School, D-45122 Essen, Germany.

出版信息

Cancer Res. 2002 Jul 1;62(13):3598-602.

PMID:12097259

Abstract

The recently discovered p53-family member p73 displays significant homology to p53, but data from primary tumors and knockout mice argue against p73 being a classical tumor suppressor. We report on the overexpression of NH(2)-terminally truncated, transactivation-deficient p73 proteins (DeltaTA-p73) in human cancer cells. Moreover, we show that DeltaTA-p73 overexpression results in malignant transformation of NIH3T3 fibroblasts and tumor growth in nude mice, thereby providing the experimental evidence for an oncogenic function of DeltaTA-p73. Apparently, increased expression of NH(2)-terminally truncated p73 isoforms conveys the TP73 gene with oncogenic activity that appears to be actively selected for during tumor development.

摘要

最近发现的p53家族成员p73与p53表现出显著的同源性，但来自原发性肿瘤和基因敲除小鼠的数据表明p73并非典型的肿瘤抑制因子。我们报道了在人类癌细胞中氨基端截短、缺乏反式激活功能的p73蛋白（DeltaTA-p73）的过表达。此外，我们发现DeltaTA-p73的过表达导致NIH3T3成纤维细胞发生恶性转化，并在裸鼠体内形成肿瘤，从而为DeltaTA-p73的致癌功能提供了实验证据。显然，氨基端截短的p73亚型的表达增加赋予了TP73基因致癌活性，这种活性在肿瘤发展过程中似乎被积极选择。