ADAM28 is overexpressed in human non-small cell lung carcinomas and correlates with cell proliferation and lymph node metastasis
ADAM28 is overexpressed in human non-small cell lung carcinomas and correlates with cell proliferation and lymph node metastasis
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DOI：
10.1002/ijc.21324
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发表时间：
2006-01-15
影响因子：
6.4
通讯作者：
Okada, Y
中科院分区：
文献类型：
--
作者：
Ohtsuka, T;Shiomi, T;Okada, Y
ADAM（a disintegrin and metalloproteinases）是最近发现的一个与蛇毒金属蛋白酶的replysin家族具有序列相似性的蛋白质基因家族，大约三分之一的家族成员在其金属蛋白酶结构域中具有催化位点的共有序列。我们采用RT-PCR方法检测了11种可能具有金属蛋白酶活性的ADAM基因在人非小细胞肺癌中的mRNA表达，发现原型膜锚定型ADAM 28（ADAM 28 m）和分泌型ADAM 28（ADAM 28 s）在肺癌组织中主要表达。实时荧光定量PCR检测结果显示，ADAM 28 m和ADAM 28 s在癌组织中的表达水平分别是非癌组织的16.8倍和9.0倍，差异有统计学意义。直径>30 mm癌组织中ADAM 28 m和ADAM 28 s的表达水平明显高于直径>30 mm癌组织。在有淋巴结转移的癌组织中表达水平也显著高于无淋巴结转移者。癌组织中MIBI阳性细胞指数与ADAM 28 m和ADAM 28 s的表达呈正相关（r分别为0.667和0.535，P <0.001）。原位杂交和免疫组化结果表明，ADAM 28主要表达于癌细胞中。Inummoblot分析显示癌组织中存在活化形式的ADAM 28。这些数据首次证明了ADAM 28在人非小细胞肺癌中过表达和激活，并表明ADAM 28在人肺癌的细胞增殖和进展中起作用的可能性。(c)2005年威利-利斯。Inc.
ADAM (a disintegrin and metalloproteinases) are a recently discovered gene family of proteins with sequence similarity to the reprolysin family of snake venom metalloproteinases, and about one-third of the family members have the catalytic site consensus sequence in their metalloproteinase domains. We screened the mRNA expression of 11 different ADAM species with putative metalloproteinase activity in human non-small cell lung carcinomas by RT-PCR, and found that prototype membrane-anchored ADAM28 (ADAM28m) and secreted ADAM28 (ADAM28s) are predominantly expressed in the carcinoma tissues. Real-time quantitative PCR demonstrated that the expression levels of ADAM28m and ADAM28s are significantly 16.8-fold and 9.0-fold higher in the carcinomas than in the non-carcinoma tissues, respectively. In addition, the expression levels of ADAM28m and ADAM28s were significantly higher in the carcinomas with >30 mm in diameter than in those ! 30 mm. The expression levels were also significantly higher in the carcinomas with lymph node metastasis than in those without metastasis. MIBI-positive cell index of the carcinomas had a direct correlation with the expression levels of ADAM28m and ADAM28s (r = 0.667, p < 0.001 and r = 0.535, p < 0.01, respectively). In situ hybridization and inummohisto-chemistry demonstrated that ADAM28 is expressed predominantly in the carcinoma cells. Inummoblot analysis showed the activated form of ADAM28 in the carcinoma tissues. These data demonstrate for the first time that ADAM28 is overexpressed and activated in human non-small cell lung carcinomas, and suggest the possibility that ADAM28 plays a role in cell proliferation and progression of the human lung carcinomas. (c) 2005 Wiley-Liss. Inc.