Altered gene and protein expression by Nm23-H1 in metastasis suppression.
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.
Women's Cancers Section, Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, 37 Convent Drive, Room 1122, Bethesda, MD 20892, USA.
Jong Heun
JH
Lee
Jean-Claude
JC
Marshall
Patricia S
PS
Steeg
Christine E
CE
Horak
D000818:Animals; D002465:Cell Movement / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D054778:NM23 Nucleoside Diphosphate Kinases / Q000235:genetics / Q000378:metabolism*; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000473:pathology; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology
D054778:NM23 Nucleoside Diphosphate Kinases