Binas B, Gusterson B, Wallace R, Clark A J
Division of Molecular Biology, Roslin Institute, Midlothian, Scotland, UK.
Dev Genet. 1995;17(2):167-75. doi: 10.1002/dvg.1020170208.
Cardiac fatty acid binding protein (cFABP) is abundantly expressed in the nondividing, functionally differentiated mammary epithelium. It is very closely related, if not identical to, a previously described protein termed mammary derived growth inhibitor (MDGI). In vitro studies suggest that low concentrations of diffusible cFABP/MDGI may play a hormone-like role in limiting proliferative activity and promoting functional differentiation of this tissue, but no in vivo data to support this idea have been published. To test this hypothesis, we compared the levels of cFABP mRNA with both the epithelial DNA labelling index and levels of beta-casein mRNA in wild-type mice. We also investigated the effect of a precocious experimental increase of cFABP levels in the mammary gland of transgenic mice on the labelling index and beta-casein mRNA levels. This was accomplished by expressing a bovine cFABP cDNA under the control of the ovine beta-lactoglobulin (BLG) gene promoter. We found that although both the DNA labelling index, beta-casein mRNA levels, and cFABP mRNA levels in wild-type mice are developmentally regulated, they do not correlate with each other during early pregnancy in individual mice. Moreover, a three- to fourfold increase of total cFABP mRNA in two transgenic lines did not affect the DNA labelling index or the levels of beta-casein mRNA, an established marker of differentiation of the mammary epithelium, at this developmental stage. These data suggest that epithelial DNA synthesis, beta-casein gene expression, and expression of the cFABP gene are regulated independently in the proliferatively active mammary gland and that the rapidly dividing mammary epithelial cells are not susceptible to the action of cFABP during early pregnancy.
心脏脂肪酸结合蛋白（cFABP）在不进行分裂、功能已分化的乳腺上皮中大量表达。它与先前描述的一种名为乳腺衍生生长抑制因子（MDGI）的蛋白质密切相关，甚至可以说完全相同。体外研究表明，低浓度的可扩散cFABP/MDGI可能在限制该组织的增殖活性和促进其功能分化方面发挥类似激素的作用，但尚未有支持这一观点的体内数据发表。为了验证这一假设，我们比较了野生型小鼠中cFABP mRNA水平与上皮细胞DNA标记指数以及β-酪蛋白mRNA水平。我们还研究了转基因小鼠乳腺中cFABP水平过早实验性升高对标记指数和β-酪蛋白mRNA水平的影响。这是通过在绵羊β-乳球蛋白（BLG）基因启动子的控制下表达牛cFABP cDNA来实现的。我们发现，尽管野生型小鼠中的DNA标记指数、β-酪蛋白mRNA水平和cFABP mRNA水平在发育过程中受到调节，但在个体小鼠怀孕早期，它们彼此之间并无关联。此外，在两个转基因品系中，总cFABP mRNA增加了三到四倍，在这个发育阶段，并未影响DNA标记指数或β-酪蛋白mRNA水平（乳腺上皮分化的一个既定标志物）。这些数据表明，在增殖活跃的乳腺中，上皮细胞DNA合成、β-酪蛋白基因表达和cFABP基因表达是独立调节的，并且在怀孕早期，快速分裂的乳腺上皮细胞对cFABP的作用不敏感。
