SLIT2, a human homologue of the Drosophila Slit2 gene, has tumor suppressor activity and is frequently inactivated in lung and breast cancers.
SLIT2, a human homologue of the Drosophila Slit2 gene, has tumor suppressor activity and is frequently inactivated in lung and breast cancers.
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发表时间：
2002-10
期刊：
影响因子：
11.2
通讯作者：
A. Dallol;N. F. da Silva;P. Viacava;J. Minna;I. Bièche;E. Maher;F. Latif
中科院分区：
文献类型：
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作者：
A. Dallol;N. F. da Silva;P. Viacava;J. Minna;I. Bièche;E. Maher;F. Latif
Slit2通过Robo受体信号传导，在轴突引导中起着至关重要的作用。最近的证据表明，Slit2蛋白可能在其他情况下发挥作用，因为人类和非洲爪蟾的Slit2已被证明可以抑制白细胞趋化性。SLIT2蛋白被认为是ROBO受体的配体。我们最近证明，在三种乳腺肿瘤系（SLIT2表达缺失或低表达）中，70%的集落生长中，启动子区域超甲基化使ROBO1失活。由于SLIT2主要是一种分泌蛋白，因此SLIT2条件培养基对几种SLIT2表达缺失或弱的乳腺癌细胞系的生长抑制作用为26-51%，但对表达正常水平SLIT2的乳腺癌细胞系没有显著影响。这些发现表明SLIT2在肺癌和乳腺癌中经常因启动子区域超甲基化和等位基因丢失而失活，并且是先前定位于4p15.2的肺癌和乳腺癌肿瘤抑制基因的优秀候选基因。
Slit2 plays a vital role in axon guidance by signaling through Robo receptors. Recent evidence suggests that Slit2 protein may function in other settings because human and Xenopus Slit2 has been shown to inhibit leukocyte chemotaxis. SLIT2 protein is a putative ligand for the ROBO receptors. We recently demonstrated that ROBO1 is inactivated by promoter region hypermethylation in 70% of colony growth in each of three breast tumor lines (with either absent or low SLIT2 expression). Because SLIT2 is primarily a secreted protein, SLIT2-conditioned medium suppressed the growth of several breast cancer lines (with absent or weak SLIT2expression) by 26-51% but had no significant effect on a breast tumor cell line that expresses normal levels of SLIT2. These findings demonstrate that SLIT2 is frequently inactivated in lung and breast cancer by promoter region hypermethylation and allele loss and is an excellent candidate for the lung and breast tumor suppressor gene previously mapped to 4p15.2.