LAPSER1:: a novel candidate tumor suppressor gene from 10q24.3
LAPSER1:: a novel candidate tumor suppressor gene from 10q24.3
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DOI：
10.1038/sj.onc.1204866
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发表时间：
2001-10-11
期刊：
影响因子：
8
通讯作者：
Chinault, AC
中科院分区：
文献类型：
--
作者：
Cabeza-Arvelaiz, Y;Thompson, TC;Chinault, AC
在包括前列腺在内的不同肿瘤组织中进行的大量 LOH 和突变分析研究表明，人类染色体 8p21-22 和 10q23-24 区域内存在多个肿瘤抑制基因 (TSG)。最近，我们发现 LZTS1（或 FEZ1）（一种假定的位于 8p22 上的 TSG）具有作为细胞生长调节剂的潜力。我们在此报告 LZTS1 相关基因 LAPSER1 的克隆、基因组织、cDNA 序列表征和表达分析。该基因位于人类染色体 10q24.3 的一个亚区域内，据报道，该区域在包括前列腺肿瘤在内的各种癌症中被删除，其频率与邻近的 PTEN 位点一样频繁。完整的 LAPSER1 cDNA 序列编码预测的蛋白质，其中包含与转录因子（P-Box、富含 Q 和多个亮氨酸拉链）中常见的结构域类似的各种结构域。 LAPSER1 在正常前列腺和睾丸中表达水平最高，存在多种亚型，其中一些亚型在某些前列腺肿瘤组织和细胞系中无法检测到或存在差异表达。 LAPSER1 cDNA 的过度表达强烈抑制了所评估的大多数癌细胞的细胞生长和集落形成效率。这些数据共同表明，LAPSER1 是另一个参与细胞生长调节的基因，其功能丧失可能会导致癌症的发生。
Numerous LOH and mutation analysis studies in different tumor tissues, including prostate, indicate that there are multiple tumor suppressor genes (TSGs) present within the human chromosome 8p21-22 and 10q23-24 regions. Recently, we showed that LZTS1 (or FEZ1), a putative TSG located on 8p22, has the potential to function as a cell growth modulator. We report here the cloning, gene organization, cDNA sequence characterization and expression analysis of LAPSER1, an LZTS1-related gene. This gene maps within a subregion of human chromosome 10q24.3 that has been reported to be deleted in various cancers, including prostate tumors, as frequently as the neighboring PTEN locus. The complete LAPSER1 cDNA sequence encodes a predicted protein containing various domains resembling those typically found in transcription factors (P-Box, Q-rich and multiple leucine zippers). LAPSER1 is expressed at the highest levels in normal prostate and testis, where multiple isoforms are seen, some of which are either undetectable or differentially expressed in some prostate tumor tissues and cell lines. Over-expression of LAPSER1 cDNA strongly inhibited cell growth and colony-forming efficiencies of most cancer cells assessed. Together these data suggest that LAPSER1 is another gene involved in the regulation of cell growth whose loss of function may contribute to the development of cancer.