Lakso M, Steeg P S, Westphal H
Laboratory of Mammalian Genes and Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.
Cell Growth Differ. 1992 Dec;3(12):873-9.
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.
在几种啮齿动物肿瘤模型系统以及人类浸润性导管乳腺癌和肝细胞癌中，非转移性（nm）23基因的表达与转移潜能呈负相关。由于肿瘤细胞的侵袭和转移涉及正常细胞在发育过程中展现出的许多过程，我们研究了nm23在小鼠胚胎发育过程中是否表达。对胚胎RNA的Northern印迹分析表明，nm23基因转录在胚胎发育过程中广泛发生。免疫组织化学分析显示，在器官发生开始时，Nm23蛋白的量在整个胚胎中相对较低且均匀。在胚胎第E10.5天，该蛋白开始优先在发育中的神经系统和心脏中积累，这是最早分化的胚胎组织。在胚胎发育过程中，肝脏、肾脏、皮肤、肠道、肾上腺和胃（但不包括肺）上皮细胞随后的分化伴随着Nm23蛋白表达的增加。尽管大多数组织在成年期仍保持Nm23蛋白水平，但在肠道上皮中这种增加是短暂的，在成年乳腺组织中在怀孕和哺乳期间呈周期性变化。我们得出结论，在发育中的小鼠中，Nm23蛋白的积累与多种上皮组织的功能分化同时发生。
