Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Oncogene. 2012 Jul 5;31(27):3287-97. doi: 10.1038/onc.2011.491. Epub 2011 Oct 24.
The B-cell translocation gene 3 (BTG3) is a member of the antiproliferative BTG gene family and a downstream target of p53. BTG3 also binds and inhibits E2F1. Although it connects functionally two major growth-regulatory pathways, the physiological role of BTG3 remains largely uncharacterized. Here, we present evidence that loss of BTG3 in normal cells induced cellular senescence, which was correlated with enhanced ERK-AP1 signaling and elevated expression of the histone H3K27me3 demethylase JMJD3/KDM6B, leading to acute induction of p16(INK4a). Importantly, we also found that BTG3 expression is specifically downregulated in prostate cancer, thus providing a physiological link with human cancers. Our data suggest that BTG3 may have a fail-safe role against tumorigenic progression.
B 细胞易位基因 3（BTG3）是一种具有抗增殖作用的 BTG 基因家族成员，也是 p53 的下游靶标。BTG3 还可以结合并抑制 E2F1。尽管它在功能上连接了两个主要的生长调节途径，但 BTG3 的生理作用在很大程度上仍未被阐明。在这里，我们提供的证据表明，正常细胞中 BTG3 的缺失会诱导细胞衰老，这与增强的 ERK-AP1 信号和组蛋白 H3K27me3 去甲基化酶 JMJD3/KDM6B 的表达升高有关，从而导致 p16(INK4a)的急性诱导。重要的是，我们还发现 BTG3 在前列腺癌中特异性地下调，从而与人类癌症建立了生理联系。我们的数据表明，BTG3 可能在防止肿瘤发生方面具有失效保护作用。
