Deleted in liver cancer 3 (DLC-3), a novel Rho GTPase-activating protein, is downregulated in cancer and inhibits tumor cell growth
Deleted in liver cancer 3 (DLC-3), a novel Rho GTPase-activating protein, is downregulated in cancer and inhibits tumor cell growth
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DOI：
10.1038/sj.onc.1210244
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发表时间：
2007-07-01
期刊：
影响因子：
8
通讯作者：
Popescu, N. C.
中科院分区：
文献类型：
--
作者：
Durkin, M. E.;Ullmannova, V.;Popescu, N. C.
两个相关的Rho gtpase激活蛋白，DLC-1（在肝癌1中缺失）和DLC-2，正在成为研究的重点。抑制癌细胞生长的肿瘤抑制基因。在本报告中，我们鉴定了Xq13染色体上编码DLC-3（也称为KIAA0189和STARD8）的基因，DLC家族的第三个成员。DLC-3基因的转录本有50个末端，其中一个末端DLC-3a编码一个1103个氨基酸的多肽，与DLC-1和DLC-2高度相似。第二个同工异构体（DLC-3b）将产生缺乏n端不育α基序结构域的蛋白质。DLC-3基因在正常组织中广泛表达，但在乳腺癌、卵巢癌、肝癌和前列腺癌细胞系中，DLC-3 mRNA水平低或缺失。使用癌症专家。在肾、肺、卵巢癌、子宫癌和乳腺癌样本中，DLC-3 mRNA表达下调。通过定量逆转录酶聚合酶链反应，DLC-3在原发性前列腺癌中的表达较正常前列腺组织降低。用DLC-3a表达载体转染人乳腺癌和前列腺癌细胞，可抑制软琼脂细胞增殖、集落形成和生长。这些结果表明，DLC-3的失调可能有助于乳腺和前列腺肿瘤的发生。
Two related Rho GTPase-activating proteins, DLC-1 (deleted in liver cancer 1) and DLC-2, are emerging as bona. de tumor suppressor genes that inhibit cancer cell growth. In this report, we characterized a gene on chromosome Xq13 that encodes DLC-3 (also known as KIAA0189 and STARD8), a third member of the DLC family. The DLC-3 gene has transcripts with alternative 50 ends, one of which, DLC-3a, encodes an 1103-amino acid polypeptide highly similar to DLC-1 and DLC-2. A second isoform (DLC-3b) would yield a protein lacking the N-terminal sterile alpha motif domain. The DLC-3 gene is widely expressed in normal tissues, but DLC-3 mRNA levels were low or absent in a significant number of breast, ovarian, liver and prostate cancer cell lines. Using a cancer pro. ling array to compare matched tumor and normal human tissues, downregulation of DLC-3 mRNA was observed in kidney, lung, ovarian, uterine and breast cancer samples. By quantitative reverse transcriptase polymerase chain reaction, DLC-3 expression was reduced in primary prostate carcinomas relative to normal prostate tissue. Transfection of human breast and prostate cancer cells with a DLC-3a expression vector inhibited cell proliferation, colony formation and growth in soft agar. These results indicate that deregulation of DLC-3 may contribute to breast and prostate tumorigenesis.