Human PARM-1 is a novel mucin-like, androgen-regulated gene exhibiting proliferative effects in prostate cancer cells
Human PARM-1 is a novel mucin-like, androgen-regulated gene exhibiting proliferative effects in prostate cancer cells
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DOI：
10.1002/ijc.23185
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发表时间：
2008-03-15
影响因子：
6.4
通讯作者：
Bakke, Oddmund
中科院分区：
文献类型：
--
作者：
Fladeby, Cathrine;Gupta, Shailly N.;Bakke, Oddmund
在本文中，我们描述了hPARM-1，大鼠PARM-1（前列腺雄激素抑制信息-1）的人类同源物，并证明了它在前列腺癌中的作用。免疫荧光显微镜和超微结构分析显示hPARM-1定位于高尔基体、质膜和早期内噬途径，但不定位于溶酶体。生化和去糖基化研究表明，hPARM-1是一种高度糖基化的粘蛋白样I型跨膜蛋白。分析hPARM-1在人体各种组织中的表达，发现其存在于大多数人体组织中，在心脏、肾脏和胎盘中表达量尤其高。雄激素控制着该基因的表达，雄激素依赖性前列腺癌细胞系LNCaP在雄激素刺激下显著增加7倍。去势后CWR22异种移植物中表达的减少进一步支持了这一点。此外，hPARM-1在PC3前列腺癌细胞中的异位表达增加了集落的形成，提示其可能在细胞增殖中起作用。这些结果提示hPARM-1可能在前列腺细胞的正常生物学和前列腺癌中起作用。(C) 2007 Wiley-Liss, Inc。
In this paper we characterize hPARM-1, the human ortholog of rat PARM-1 (prostatic androgen-repressed message-1) and demonstrate its role in prostate cancer. Immunofluorescence microscopy and ultrastructural analysis revealed the localization of hPARM-1 to Golgi, plasma membrane and the early endocytic pathway but not in lysosomes. Biochemical and deglycosylation studies showed hPARM-1 as a highly glycosylated, mucin-like type I transmembrane protein. Analysis of expression of hPARM-1 in various human tissues revealed its presence in most human tissues with especially high expression in heart, kidney and placenta. Androgen controls the expression of the gene as a marked 7-fold increase is seen in the androgen-dependent prostate cancer cell line, LNCaP on androgen stimulation. This is further supported by its decrease in expression in CWR22 xenograft upon castration. Moreover, ectopic expression of hPARM-1 in PC3 prostate cancer cells increased colony formation, suggesting a probable role in cell proliferation. These results suggest that hPARM-1 may have a role in normal biology of the prostate cell and in prostate cancer. (C) 2007 Wiley-Liss, Inc.