Altered gene and protein expression by Nm23-H1 in metastasis suppression

作     者：Lee, Jong Heun Marshall, Jean-Claude Steeg, Patricia S. Horak, Christine E. 

作者机构：NCI Womens Canc Sect Mol Pharmacol Lab Ctr Canc Res Bethesda MD 20892 USA 

出 版 物：《MOLECULAR AND CELLULAR BIOCHEMISTRY》 (分子与细胞生物化学)

年 卷 期：2009年第329卷第1-2期

页      面：141-148页

核心收录：

学科分类：0710[理学-生物学] 071010[理学-生物化学与分子生物学] 07[理学] 

基　　金：Intramural NIH HHS [Z01 SC000892-24  Z01 SC000892] Funding Source: Medline 

主　　题：Nm23 Metastasis suppressor genes Gene expression 

摘      要：Metastasis suppressor genes (MSG) are characterized by their ability to inhibit the formation of metastasis, while not affecting the growth of the primary tumor in vivo. Nm23-H1, the first MSG to be characterized, has been shown to alter both gene and protein expression in cancer cells. Recently, microarray expression profiling revealed that Nm23-H1 downregulated EDG2, which encodes for a lysophosphatidic acid (LPA) receptor. Reintroduction of EDG2 into cells that express Nm23-H1 overcame the metastasis suppressive ability of Nm23-H1 in both in vivo pulmonary colonization and spontaneous metastasis assays. In addition, isotope capture affinity tag (ICAT) proteomic analysis was performed to identify differentially expressed proteins not accounted for by microarray analysis. ICAT identified several differentially regulated proteins, including GEMIN5, a protein involved in differential mRNA splicing. The contribution of alternative mRNA splicing to cancer and cancer metastasis is poorly defined. It is possible that Nm23-H1, through the regulation of RNA processing proteins, may play a role in proteome stability.