Translational approaches using metastasis suppressor genes.
Cancer metastasis is a significant contributor to breast cancer patient morbidity and mortality. In order to develop new anti-metastatic therapies, we need to understand the biological and biochemical mechanisms of metastasis. Toward these efforts, we and others have studied metastasis suppressor genes, which halt metastasis in vivo without affecting primary tumor growth. The first metastasis suppressor gene identified was nm23, also known as NDP kinase. Nm23 represents the most widely validated metastasis suppressor gene, based on transfection and knock-out mouse strategies. The biochemical mechanism of metastasis suppression via Nm23 is unknown and likely complex. Two potential mechanisms include binding proteins and a histidine kinase activity. Elevation of Nm23 expression in micrometastatic tumor cells may constitute a translational strategy for the limitation of metastatic colonization in high risk cancer patients. To date, medroxyprogesterone acetate (MPA) has been identified as a candidate compound for clinical testing.
Palmieri
Diane
D
Women's Cancers Section, Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, Building 37, Room 1122, NIH, Bethesda, MD 20892, USA.
Horak
Christine E
CE
Lee
Jong-Heun
JH
Halverson
Douglas O
DO
Steeg
Patricia S
PS
D000818:Animals; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D000071677:Histidine Kinase; D006801:Humans; D017258:Medroxyprogesterone Acetate; D051379:Mice; D018345:Mice, Knockout; D016297:Mutagenesis, Site-Directed; D054778:NM23 Nucleoside Diphosphate Kinases; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000517:prevention & control; D009701:Nucleoside-Diphosphate Kinase / Q000235:genetics* / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism
D054778:NM23 Nucleoside Diphosphate Kinases; D017258:Medroxyprogesterone Acetate; D011494:Protein Kinases; D000071677:Histidine Kinase; C517938:NME1 protein, human; C517939:Nme1 protein, mouse; D009701:Nucleoside-Diphosphate Kinase