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Insulin regulates human mammosphere development and function

机译:胰岛素调节人类乳腺圈的发展和功能

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Assessing the role of lactogenic hormones in human mammary gland development is limited due to issues accessing tissue samples and so development of a human in vitro three-dimensional mammosphere model with functions similar to secretory alveoli in the mammary gland can aid to overcome this shortfall. In this study, a mammosphere model has been characterised using human mammary epithelial cells grown on either mouse extracellular matrix or agarose and showed insulin is essential for formation of mammospheres. Insulin was shown to up-regulate extracellular matrix genes. Microarray analysis of these mammospheres revealed an up-regulation of differentiation, cell-cell junctions, and cytoskeleton organisation functions, suggesting mammosphere formation may be regulated through ILK signalling. Comparison of insulin and IGF-1 effects on mammosphere signalling showed that although IGF-1 could induce spherical structures, the cells did not polarise correctly as shown by the absence of up-regulation of polarisation genes and did not induce the expression of milk protein genes. This study demonstrated a major role for insulin in mammary acinar development for secretory differentiation and function indicating the potential for reduced lactational efficiency in women with obesity and gestational diabetes.
机译:由于获取组织样本的问题,评估催乳激素在人类乳腺发育中的作用是有限的,因此开发具有类似于乳腺分泌小泡功能的人体体外三维乳腺球模型有助于克服这一不足。在这项研究中,使用在小鼠细胞外基质或琼脂糖上生长的人乳腺上皮细胞对乳腺球模型进行了表征,并表明胰岛素对乳腺球的形成至关重要。胰岛素可以上调细胞外基质基因。对这些乳腺球的微阵列分析显示分化、细胞间连接和细胞骨架组织功能上调,表明乳腺球的形成可能通过ILK信号调节。比较胰岛素和IGF-1对乳腺信号传导的影响表明,尽管IGF-1可以诱导球形结构,但细胞没有正确极化,极化基因没有上调,也没有诱导乳蛋白基因的表达。这项研究表明,胰岛素在乳腺腺泡发育中的主要作用是分泌分化和功能,这表明肥胖和妊娠期糖尿病妇女的泌乳效率可能降低。

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