Molecular cloning and characterization of STAMP2, an androgen-regulated six transmembrane protein that is overexpressed in prostate cancer
Molecular cloning and characterization of STAMP2, an androgen-regulated six transmembrane protein that is overexpressed in prostate cancer
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DOI：
10.1038/sj.onc.1208677
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发表时间：
2005-07-21
期刊：
影响因子：
8
通讯作者：
Saatcioglu, F
中科院分区：
文献类型：
--
作者：
Korkmaz, CG;Korkmaz, KS;Saatcioglu, F
我们发现了一个新的基因，6个前列腺癌跨膜蛋白2(STAMP2)，它与最近发现的STAMP1基因有很高的序列相似性。STAMP2是一种组织限制性表达蛋白，在胎盘、肺、心脏和前列腺中的表达水平最高，预计编码一个459个氨基酸的六跨膜蛋白。用一种绿色荧光蛋白(GFP)标记的STAMP2在定量时间推移和免疫荧光共聚焦显微镜下显示，STAMP2主要定位于高尔基复合体、反高尔基网络和质膜。STAMP 2也定位于胞浆中的泡状-管状结构，并与早期内体抗原1(EEA1)共存，提示它可能参与了分泌/内吞途径。在雄激素敏感、雄激素受体阳性的前列腺癌细胞系LNCaP中，STAMP2的表达受到精致的雄激素调节，但在雄激素受体阴性的前列腺癌细胞系PC-3和DU145中则没有。对匹配的正常组织和前列腺癌标本显微切割的肿瘤标本中STAMP2表达的分析表明，与正常前列腺上皮细胞相比，STAMP2在前列腺癌细胞中过表达。此外，STAMP2在前列腺癌细胞中的异位表达显著促进细胞生长和集落形成，提示STAMP2可能在细胞增殖中起作用。综上所述，这些数据表明，STAMP2可能有助于前列腺细胞的正常生物学，以及前列腺癌的进展。
We have identified a novel gene, six transmembrane protein of prostate 2 (STAMP2), named for its high sequence similarity to the recently identified STAMP1 gene. STAMP2 displays a tissue-restricted expression with highest expression levels in placenta, lung, heart, and prostate and is predicted to code for a 459-amino acid six transmembrane protein. Using a form of STAMP2 labeled with green flourescent protein (GFP) in quantitative time-lapse and immuno fluorescence confocal microscopy, we show that STAMP2 is primarily localized to the Golgi complex, trans-Golgi network, and the plasma membrane. STAMP 2 also localizes to vesicular-tubular structures in the cytosol and colocalizes with the Early Endosome Antigen1 (EEA1) suggesting that it may be involved in the secretory/endocytic pathways. STAMP2 expression is exquisitely androgen regulated in the androgen-sensitive, androgen receptor-positive prostate cancer cell line LNCaP, but not in androgen receptor-negative prostate cancer cell lines PC-3 and DU145. Analysis of STAMP2 expression in matched normal and tumor samples microdissected from prostate cancer specimens indicates that STAMP2 is overexpressed in prostate cancer cells compared with normal prostate epithelial cells. Further more, ectopic expression of STAMP2 in prostate cancer cells significantly increases cell growth and colony formation suggesting that STAMP2 may have a role in cell proliferation. Taken together, these data suggest that STAMP2 may contribute to the normal biology of the prostate cell, as well as prostate cancer progression.