Cell adhesion and prostate tumor-suppressor activity of TSLL2/IGSF4C, an immunoglobulin superfamily molecule homologous to TSLC1/IGSF4
Cell adhesion and prostate tumor-suppressor activity of TSLL2/IGSF4C, an immunoglobulin superfamily molecule homologous to TSLC1/IGSF4
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DOI：
10.1038/sj.onc.1209192
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发表时间：
2006-03-01
期刊：
影响因子：
8
通讯作者：
Murakami, Y
中科院分区：
文献类型：
--
作者：
Williams, YN;Masuda, M;Murakami, Y
TSLL2/IGSF4C 编码免疫球蛋白 (Ig) 超家族分子，与肺肿瘤抑制因子 TSLC1 具有显着同源性。 55 kDa的TSLL2蛋白除大脑外主要在肾脏、膀胱和前列腺中表达。在这里，我们报告了 TSLL2 在泌尿组织中的生物学意义。免疫组织化学研究表明，TSLL2 在肾小管、膀胱移行上皮和前列腺腺上皮的细胞附着位点表达。共聚焦显微镜分析表明，TSLL2 位于偏振 Mardin-Darby 犬肾 (MDCK) 细胞的侧膜中。 TSLL2 形成同源二聚体，其过度表达以不依赖 Ca2+/Mg2+ 的方式诱导悬浮的 MDCK 细胞聚集，表明它通过同源反式相互作用参与细胞粘附。 TSLL2 基因定位于染色体区域 19q13.2，其杂合性缺失在前列腺癌中经常被报道。 TSLL2 蛋白在九种原发性前列腺癌中的九种以及前列腺癌细胞 PPC-1 中丢失。将 TSLL2 引入 PPC-1 可以强烈抑制裸鼠皮下肿瘤的形成。这些结果表明，TSLL2 是 Ig 超家族细胞粘附分子的新成员，并且是前列腺癌的肿瘤抑制候选者。
The TSLL2/ IGSF4C encodes an immunoglobulin (Ig) superfamily molecule showing significant homology with a lung tumor suppressor, TSLC1. The TSLL2 protein of 55 kDa is mainly expressed in the kidney, bladder, and prostate in addition to the brain. Here, we report the biological signifance of TSLL2 in the urinary tissues. An immunohistochemical study reveals that TSLL2 is expressed at the cell-cell attachment sites in the renal tubules, the transitional epithelia of the bladder, and the glandular epithelia of the prostate. Confocal microscopy analysis demonstrates that TSLL2 is localized in the lateral membranes in polarized Mardin-Darby canine kidney (MDCK) cells. TSLL2 forms homo-dimers and its overexpression induces aggregation of suspended MDCK cells in a Ca2+/Mg2+ -independent manner, suggesting that it is involved in cell adhesion through homophilic trans-interaction. The TSLL2 gene is mapped on the chromosomal region 19q13.2, whose loss of heterozygosity has been frequently reported in prostate cancer. TSLL2 protein is lost in nine of nine primary prostate cancers and in a prostate cancer cell, PPC-1. Introduction of TSLL2 into PPC-1 strongly suppresses subcutaneous tumor formation in nude mice. These results suggest that TSLL2 is a new member of the Ig superfamily cell adhesion molecules and is a tumor-suppressor candidate in prostate cancer.