Embryonic expression of nm23 during mouse organogenesis.

Nonmetastatic (nm) 23 gene expression correlates inversely with metastatic potential in several rodent tumor model systems as well as in human infiltrating ductal breast and hepatocellular carcinomas. Since tumor cell invasion and metastasis involve many processes exhibited by normal cells during development, we investigated whether nm23 is expressed during mouse embryogenesis. Northern blot analysis of embryonic RNAs showed that nm23 gene transcription occurs widely during embryogenesis. Immunohistochemical analysis demonstrated that, at the onset of organogenesis, the amount of Nm23 protein is relatively low and uniform throughout the embryo. On embryonic day E10.5, the protein begins to accumulate preferentially in the developing nervous system and heart, the first embryonic tissues to differentiate. Subsequent differentiation of liver, kidney, skin, intestine, adrenal, and stomach (but not lung) epithelial cells during embryonic development is accompanied by increased Nm23 protein expression. Although most tissues retain Nm23 protein levels to adult life, the increase is transient in intestinal epithelia and cyclic in adult mammary tissue during pregnancy and lactation. We conclude that Nm23 protein accumulation is coincident with the functional differentiation of multiple epithelial tissues in the developing mouse.