HTPAP gene on chromosome 8p is a candidate metastasis suppressor for human hepatocellular carcinoma
HTPAP gene on chromosome 8p is a candidate metastasis suppressor for human hepatocellular carcinoma
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DOI：
10.1038/sj.onc.1209191
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发表时间：
2006-03
期刊：
影响因子：
8
通讯作者：
X. Wu;H. Jia;Y. Wang;N. Ren;Q. Ye;Hc Sun;L. Wang;Y.-K. Liu;Z. Tang;L. Qin
中科院分区：
文献类型：
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作者：
X. Wu;H. Jia;Y. Wang;N. Ren;Q. Ye;Hc Sun;L. Wang;Y.-K. Liu;Z. Tang;L. Qin
我们的前期研究表明，染色体8 p缺失与肝细胞癌（HCC）的转移有关，其中可能存在一些新的转移抑制基因。本研究旨在鉴定转移抑制基因。利用染色体8 p的表达序列标签（expressed sequence tags，ESTs）构建cDNA芯片，比较具有不同转移潜能和相似遗传背景的MHCC 97-H和MHCC 97-L细胞系之间表达谱的差异。结果表明，在具有高转移潜能的MHCC 97-H细胞系中，有10个EST表达显著下调。在染色体8 p12处鉴定出一个全长基因HTPAP（phosphatidic acid phosphatase type 2 domain containing 1B）。序列测定和生物信息学分析表明，HTPAP基因全长826 bp，编码175个氨基酸，在NH 2端有一个跨膜区，有两个蛋白激酶C磷酸化位点和一个酪氨酸激酶磷酸化位点。在转移癌组织中的表达水平明显低于原发癌组织。体内外实验均表明HTPAP能抑制肝癌的侵袭和转移。提示HTPAP是一个新的肝癌转移抑制基因。HTPAP影响肝癌转移的机制尚不清楚，值得进一步研究。
Our previous studies suggested that chromosome 8p deletion is associated with metastasis of hepatocellular carcinoma (HCC), in which some novel metastasis suppressor genes might be harbored. The present study aimed to identify the metastatic suppressor gene (s). A cDNA chip was constructed with the expressed sequence tags (ESTs) from chromosome 8p and used to compare the difference of expression profiling between the MHCC97-H and MHCC97-L cell lines with different metastatic potentials and similar genetic backgrounds. In all, 10 ESTs were significantly downregulated in MHCC97-H cell line with higher metastatic potential. One full-length gene, HTPAP (phosphatidic acid phosphatase type 2 domain containing 1B), was identified at chromosome 8p12. Sequencing and bioinformatic analyses revealed that HTPAP has 826 bp and encodes a putative protein of 175 amino acids with a transmembrane segment at the NH2 terminus, two protein kinase C phosphorylation site and one tyrosine kinase phosphorylation site. Its expression level in metastatic tumor tissues was much lower than that of primary HCC tissues. Both in vitro and in vivo assays suggested that HTPAP could suppress the invasion and metastasis of HCC. These suggested that HTPAP is a novel metastatic suppressor gene for HCC. The mechanism of the effect of HTPAP on HCC metastasis is not clear yet and deserves further investigation.