Accession Number : ADA329399

Title :   Possible Mechanisms for Regulation of Breast Tumor Micrometastasis by NME Genes

Descriptive Note : Annual rept. 29 Apr 96-28 Apr 97

Corporate Author : NEW YORK MEDICAL COLL VALHALLA

Personal Author(s) : Backer, Joseph M.

PDF Url : ADA329399

Report Date : MAY 1997

Pagination or Media Count : 24

Abstract : Metastatic dissemination of primary breast tumors is controlled by positive and negative regulators. We found that expression of a catalytically inactive nucleoside diphosphate kinase B (NDPK B/T) in MDA-MB-435 human breast carcinoma cells significantly decreases their metastatic dissemination in a nude mouse assay. Inhibition of metastatic dissemination of primary tumors formed by these cells occurs prior to formation of detectable micrometastasis. Our structural studies suggests that wild type NDPK B and highly homologous NDPK A form different oligomers that may occupy specific binding sites We hypothesize that NDPK B/T displaces wild type NDPK B from specific binding sites, acting in effect as a dominant negative mutant. These results suggest that NDPK B acts as a positive regulator of metastatic potential of human tumor cells and that specific inhibition of NDPK B may be a target for potential anti-metastasis therapeutics.

Descriptors :   *GENES, *METASTASIS, *BREAST CANCER, HUMANS, ENZYMES, NEOPLASMS, MUTATIONS, MICE, INHIBITION, CELLS(BIOLOGY), OLIGOMERS, MAMMARY GLANDS, PHOSPHORUS TRANSFERASES, NUCLEOSIDES.

Subject Categories : Biochemistry
      Genetic Engineering and Molecular Biology
      Anatomy and Physiology
      Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE