REGULATION OF ALPHA-FETOPROTEIN GENE EXPRESSION

哺乳动物发育中胎儿血清中的主要蛋白质组分 甲胎蛋白(AFP)，是在胚胎肝脏中合成的， 卵黄囊的内脏内胚层。出生后，细胞合成的速度 肝脏中的甲胎蛋白急剧下降到几乎检测不到的水平。 未怀孕的成年人。AFP在成人肝脏中的合成在 肝再生和特定肿瘤，如肝癌和 畸胎癌。相比之下，作为主要血清的血清白蛋白 成年肝脏合成的蛋白质，从早期的低水平增加 出生后和成人发育到较高的、相对稳定的水平 生活。这些血清蛋白在进化过程中作为基因的结果而出现。 在小鼠的5号染色体上，它们紧密相连。二 影响甲胎蛋白但不影响白蛋白转录的调控基因 在肝脏发育过程中，已经从基因上进行了描述。这些基因最近 已被证明是多功能的，因为它们影响转录 除AFP外的其他非连锁基因。我们目前正在开发 这些调控基因产物的遗传和生化分析 这将使我们能够孤立他们并确定他们的行动模式。在… 同时，组织特异性转录所需的DNA序列 体内的甲胎蛋白和白蛋白基因，使用DNA介导的基因转移到 F9畸胎癌细胞和受精卵都是 已确认身份。(M)

The major protein component in the serum of the developing mammalian fetus is alpha-fetoprotein (AFP), which is synthesized in the embryonic liver and visceral endoderm of the yolk sac. After birth, the rate of synthesis of AFP in liver decreases drastically to levels that are barely detectable in nonpregnant adults. Synthesis of AFP is resumed in adult liver during liver regeneration and in specific tumors such as hepatomas and teratocarcinomas. In contrast, serum albumin, which is the major serum protein synthesized by the adult liver, increases from low levels early in development, to high, relatively constant levels after birth and in adult life. These serum proteins arose in evolution as the consequence of a gene duplication and are tightly linked in tandem on chromosome 5 in mice. Two transacting regulatory genes that affect AFP, but not albumin transcription in developing liver, have been described genetically. These genes recently have been shown to be pleiotrophic in that they affect transcription of other unlinked genes in addition to AFP. We are currently developing genetic and biochemical assays for the products of these regulatory genes that will allow us to isolate them and determine their mode of action. At the same time, the DNA sequences required for tissue-specific transcription of the AFP and albumin genes in vivo, using DNA-mediated gene transfer into both F9 teratocarcinoma cells and fertilized mouse eggs, are being identified. (M)