Tumor-suppressive functions of leucine zipper transcription factor-like 1.
Tumor-suppressive functions of leucine zipper transcription factor-like 1.
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DOI：
10.1158/0008-5472.can-09-3826
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发表时间：
2010-04-01
期刊：
影响因子：
11.2
通讯作者：
Liu ZP
中科院分区：
文献类型：
--
作者：
Wei Q;Zhou W;Wang W;Gao B;Wang L;Cao J;Liu ZP
人亮氨酸拉链转录因子1（LZTFL 1）是一个新基因，其生物学功能尚不清楚。它位于染色体3p21.3区域，是肿瘤抑制基因的热点。为了了解LZTFL 1的生物学功能，我们采用免疫组织化学方法检测了LZTFL 1在组织芯片中的肿瘤和正常组织中的表达水平，并对84例胃癌标本进行了临床存档。我们发现LZTFL 1在正常组织的上皮细胞中高度表达，并且在相应的肿瘤样品中显著下调。LZTFL 1的表达水平与患者的生存结局显著相关，与肿瘤转移呈显著负相关。LZTFL 1在肿瘤细胞中的过表达在体外抑制了非锚定依赖性细胞生长和细胞迁移，并在体内抑制了肿瘤生长。此外，我们表明，LZTFL 1的表达上调上皮细胞分化，并沿沿着肠的隐窝-绒毛轴分级，在隐窝的增殖区表达水平最低，在绒毛的分化区的顶点表达水平最高。LZTFL 1的表达与E-钙粘蛋白在质膜上的表达重叠。我们的研究结果表明，LZTFL 1是一种肿瘤抑制因子，LZTFL 1表达的缺失具有显著的临床结局。LZTFL 1的表达可作为判断胃癌患者预后的独立指标。我们认为LZTFL 1可能通过稳定E-钙粘蛋白介导的粘附连接形成和促进上皮细胞分化来抑制肿瘤发生。
Human leucine zipper transcription factor like 1 (LZTFL1) is a novel gene with unknown biological functions. It is located in the chromosome region 3p21.3, a hot spot for tumor suppressor genes. To understand the biological functions of LZTFL1, we surveyed the expression level of LZTFL1 in tumor and normal samples in tissue microarrays and a clinical archive of 84 gastric cancer specimens using immunohistochemistry. We found that LZTFL1 is expressed highly in the epithelial cells of normal tissues and is significantly down regulated in the corresponding tumor samples. The expression level of LZTFL1 correlated significantly with the survival outcomes of the patients and had significant inverse correlation with tumor metastasis. Overexpression of LZTFL1 in tumor cells inhibited anchorage-independent cell growth and cell migration in vitro, and repressed tumor growth in vivo. Furthermore, we show that LZTFL1 expression is upregulated upon epithelial cell differentiation and is graded along the crypt-villus axis of the intestine with weakest expression level in the proliferative zone of the crypt and highest expression level at the apex of the differentiation zone in the villus. Expression of LZTFL1 overlaps with that of E-cadherin at the plasma membrane. Our results indicate that LZTFL1 is a tumor suppressor and that loss of LZTFL1 expression has significant clinical outcomes. LZTFL1 expression may serve as an independent prognostic marker for survival outcome of gastric cancer patients. We propose that LZTFL1 may inhibit tumorigenesis by stabilizing E-cadherin-mediated adherens junction formation and promoting epithelial cell differentiation.