the anti-metastatic nm23-1 gene is needed for the final step of mammary duct maturation of the mouse nipple的anti-metastatic nm23-1基因需要最后一步的乳腺导管乳头成熟的老鼠.pdfVIP

The Anti-Metastatic nm23-1 Gene Is Needed for the Final Step of Mammary Duct Maturation of the Mouse Nipple 1,2 1,2 1,2 3 1,2 Camille Deplagne , Evelyne Peuchant , Isabelle Moranvillier , Pierre Dubus , Sandrine Dabernat * ´ ´ ´ ´ ´ 1 Unite U1035, INSERM, Bordeaux, France, 2 Biotherapies des maladies genetiques et cancers, Univ. Segalen Bordeaux, Bordeaux, France, 3 Equipe 2406 Histologie et ´ pathologie moleculaire des tumeurs, Univ. Segalen Bordeaux, Bordeaux, France Abstract Nm23/NDP kinases are multifunctional enzymes involved in the general homeostasis of triphosphate nucleosides. Numerous studies have shown that NDPKs also serve as regulatory factors of various cell activities, not always connected to nucleotide phosphorylation. In particular, the nme-1 gene, encoding the NM23-1/NDPKA protein, has been reported as a metastasis suppressor gene. This activity was validated in hepatocellular tumors induced in nm23-1 deficient mice. Yet, data describing the primary physiological functions of nm23-1/NDPKA is still scarce. We have characterized in depth the phenotype of nm23-1 deletion in the mammary gland in mice carrying whole body nm23-M1 invalidation. We also asked why the nm23-M12/ 2 mutant females displayed severe nursing disability. We found that the growth retardation of mutant virgin glands was due to reduced proliferation and apoptosis of the epithelial cells within