Wang Ruoxiang, He Hui, Sun Xiaojuan, Xu Jianchun, Marshall Fray F, Zhau Haiyen, Chung Leland W K, Fu Haian, He Dalin
Department of Urology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Biochem Biophys Res Commun. 2009 Nov 20;389(3):455-60. doi: 10.1016/j.bbrc.2009.08.165. Epub 2009 Sep 2.
We have reported isolation and characterization of the prostate-specific and androgen-regulated PrLZ gene abnormally expressed in prostate cancer. PrLZ is a potential biomarker for prostate cancer and a candidate oncogene promoting cell proliferation and survival in prostate cancer cells. A full delineation of the PrLZ gene and its gene products may provide clues to the mechanisms regulating its expression and function. In this report, we identified three additional exons in the PrLZ gene and recognized five transcript variants from alternative splicing that could be detected by RT-PCR and Western blotting. Structural comparison demonstrated that the PrLZ proteins are highly conserved among species. PrLZ contains multiple potential sites for interaction with other proteins. We used mammalian two-hybrid assays to demonstrate that PrLZ isoforms interact with 14-3-3 proteins, and multiple sites in the PrLZ may be involved in the interaction. Alternative splicing may contribute to abnormally enhanced PrLZ levels in prostate cancer, and interaction with 14-3-3 proteins may be a mechanism by which PrLZ promotes cell proliferation and survival during prostate cancer development and progression. This information is a valuable addition to the investigation of the oncogenic properties of the PrLZ gene.
我们已报道了在前列腺癌中异常表达的前列腺特异性且受雄激素调节的PrLZ基因的分离与特性分析。PrLZ是前列腺癌的潜在生物标志物以及促进前列腺癌细胞增殖和存活的候选癌基因。对PrLZ基因及其基因产物的全面描述可能为调节其表达和功能的机制提供线索。在本报告中，我们在PrLZ基因中鉴定出另外三个外显子，并识别出五个通过逆转录聚合酶链反应（RT-PCR）和蛋白质免疫印迹法（Western blotting）可检测到的可变剪接转录变体。结构比较表明，PrLZ蛋白在物种间高度保守。PrLZ包含多个与其他蛋白质相互作用的潜在位点。我们使用哺乳动物双杂交试验证明PrLZ同工型与14-3-3蛋白相互作用，并且PrLZ中的多个位点可能参与这种相互作用。可变剪接可能导致前列腺癌中PrLZ水平异常升高，与14-3-3蛋白的相互作用可能是PrLZ在前列腺癌发生和发展过程中促进细胞增殖和存活的一种机制。该信息是对PrLZ基因致癌特性研究的有价值补充。
