Department of Biochemistry, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
Sci Rep. 2016 Nov 17;6:37310. doi: 10.1038/srep37310.
Androgen-Induced bZIP (AIbZIP) is structurally a bZIP transmembrane transcription factor belonging to the CREB/ATF family. This molecule is highly expressed in androgen-sensitive prostate cancer cells and is transcriptionally upregulated by androgen treatment. Here, we investigated molecular mechanism of androgen-dependent expression of AIbZIP and its physiological function in prostate cancer cells. Our data showed that SAM pointed domain-containing ETS transcription factor (SPDEF), which is upregulated by androgen treatment, directly activates transcription of AIbZIP. Knockdown of AIbZIP caused a significant reduction in the proliferation of androgen-sensitive prostate cancer cells with robust expression of p21. Mechanistically, we demonstrated that AIbZIP interacts with old astrocyte specifically induced substance (OASIS), which is a CREB/ATF family transcription factor, and prevents OASIS from promoting transcription of its target gene p21. These findings showed that AIbZIP induced by the androgen receptor (AR) axis plays a crucial role in the proliferation of androgen-sensitive prostate cancer cells, and could be a novel target of therapy for prostate cancer.
雄激素诱导的 bZIP（AIbZIP）在结构上是一种 bZIP 跨膜转录因子，属于 CREB/ATF 家族。该分子在雄激素敏感的前列腺癌细胞中高度表达，并受雄激素处理的转录上调。在这里，我们研究了 AIbZIP 的雄激素依赖性表达的分子机制及其在前列腺癌细胞中的生理功能。我们的数据表明，雄激素处理上调的 SAM 点结构域包含 ETS 转录因子（SPDEF）直接激活 AIbZIP 的转录。AIbZIP 的敲低导致具有强烈 p21 表达的雄激素敏感前列腺癌细胞的增殖显著减少。在机制上，我们证明 AIbZIP 与 old astrocyte specifically induced substance（OASIS）相互作用，OASIS 是 CREB/ATF 家族转录因子，可防止 OASIS 促进其靶基因 p21 的转录。这些发现表明，雄激素受体（AR）轴诱导的 AIbZIP 在雄激素敏感的前列腺癌细胞增殖中发挥关键作用，可能成为前列腺癌治疗的新靶点。
