Mochizuki Satsuki, Okada Yasunori
Department of Pathology, School of Medicine, Keio University, Tokyo, Japan.
Curr Pharm Des. 2009;15(20):2349-58. doi: 10.2174/138161209788682424.
ADAM28 is a member of the ADAM (a disintegrin and metalloproteinase) gene family and consists of two isoforms, prototype membrane-type form and short secreted form. The metalloproteinase domain of ADAM28 has the zinc-binding consensus sequence, and ADAM28 exhibits catalytic activity to a few substrates such as insulin-like growth factor binding protein-3. The disintegrin domain interacts with integrins alpha4beta1, alpha4beta7 and alpha9beta1. In human non-small cell lung carcinomas and breast carcinomas, ADAM28 is overexpressed predominantly by carcinoma cells, and the expression correlates with carcinoma cell proliferation and lymph node metastasis. In this review we present our data on the activation of proADAM28, the tissue localization in human cancers and the interaction molecules, and discuss the regulation of ADAM28 activity and gene expression, the functions of ADAM28 in human cancers and the possibility of ADAM28 as a target for cancers.
ADAM28是ADAM（一种去整合素和金属蛋白酶）基因家族的成员，由两种异构体组成，即原型膜型和短分泌型。ADAM28的金属蛋白酶结构域具有锌结合共有序列，并且ADAM28对一些底物如胰岛素样生长因子结合蛋白-3具有催化活性。去整合素结构域与整合素α4β1、α4β7和α9β1相互作用。在人类非小细胞肺癌和乳腺癌中，ADAM28主要在癌细胞中过度表达，且该表达与癌细胞增殖和淋巴结转移相关。在本综述中，我们展示了关于proADAM28激活、在人类癌症中的组织定位以及相互作用分子的数据，并讨论了ADAM28活性和基因表达的调控、ADAM28在人类癌症中的功能以及ADAM28作为癌症靶点的可能性。
