Feng Z, Joos H J, Vallan C, Mühlbauer R, Altermatt H J, Jaggi R
Institute of Molecular and Cell Biology, National University of Singapore, Singapore.
Oncogene. 1998 Nov 19;17(20):2593-600. doi: 10.1038/sj.onc.1202195.
Apoptotic cell death was shown to be accompanied or preceded by an elevated expression of the c-fos protooncogene and DNA binding activity of transcription factor AP-1. We used Fos-deficient mice to study the role of c-Fos during programmed cell death in the prostate. In normal mice apoptosis is induced in the prostate within 2-4 days after castration. Histological features of reduced secretory activity and morphological signs of programmed cell death become obvious. No apparent decrease in secretory activity and no epithelial cell death were observed in Fos-deficient animals after castration. Fragmentation of nuclear DNA was measured by in situ terminal transferase reaction. DNA fragmentation was observed in the prostate epithelium of control mice after castration whereas no similar fragmentation was found in Fos-deficient animals. After castration an AP-1 complex accumulated in the prostate of Fos deficient mice which mainly consists of FosB, Fra-2 and JunD whereas in control animals the AP-1 complex in addition contained c-Fos. Our data strongly suggest that c-Fos is required for programmed cell death of prostate epithelial cells.
研究表明，凋亡性细胞死亡伴随着原癌基因c-fos表达的升高或先于其发生，同时转录因子AP-1的DNA结合活性也会升高。我们利用Fos基因缺陷小鼠来研究c-Fos在前列腺程序性细胞死亡过程中的作用。在正常小鼠中，去势后2至4天前列腺会诱导凋亡。分泌活性降低的组织学特征以及程序性细胞死亡的形态学迹象变得明显。去势后，在Fos基因缺陷动物中未观察到分泌活性明显降低，也未观察到上皮细胞死亡。通过原位末端转移酶反应测量核DNA片段化。去势后，在对照小鼠的前列腺上皮中观察到DNA片段化，而在Fos基因缺陷动物中未发现类似的片段化现象。去势后，Fos基因缺陷小鼠的前列腺中积累了一种AP-1复合物，该复合物主要由FosB、Fra-2和JunD组成，而在对照动物中，AP-1复合物还包含c-Fos。我们的数据强烈表明，c-Fos是前列腺上皮细胞程序性死亡所必需的。
