Leeds Institute of Medical Research, University of Leeds, St James's University Hospital, Leeds LS9 7TF, UK.
Genes (Basel). 2021 Jan 26;12(2):162. doi: 10.3390/genes12020162.
The Cub Sushi Multiple Domains-1 (CSMD1) protein is a tumour suppressor which has been shown to play a role in regulating human mammary duct development in vitro. knockdown in vitro demonstrated increased cell proliferation, invasion and motility. However, the role of Csmd1 in vivo is poorly characterised when it comes to ductal development and is therefore an area which warrants further exploration. In this study a knockout (KO) mouse model was used to identify the role of Csmd1 in regulating mammary gland development during puberty. Changes in duct development and protein expression patterns were analysed by immunohistochemistry. This study identified increased ductal development during the early stages of puberty in the KO mice, characterised by increased ductal area and terminal end bud number at 6 weeks. Furthermore, increased expression of various proteins (Stat1, Fak, Akt, Slug/Snail and Progesterone receptor) was shown at 4 weeks in the KO mice, followed by lower expression levels from 6 weeks in the KO mice compared to the wild type mice. This study identifies a novel role for Csmd1 in mammary gland development, with Csmd1 KO causing significantly more rapid mammary gland development, suggesting an earlier adult mammary gland formation.
Cub Sushi Multiple Domains-1 (CSMD1) 蛋白是一种肿瘤抑制因子,已被证明在体外调节人类乳腺导管发育中发挥作用。体外敲低 CSMD1 显示细胞增殖、侵袭和迁移增加。然而,当涉及到导管发育时,CSmd1 在体内的作用尚未得到很好的描述,因此这是一个值得进一步探索的领域。在这项研究中,使用了一种 Cub Sushi Multiple Domains-1 (CSMD1) 基因敲除 (KO) 小鼠模型来确定 CSMD1 在调节青春期乳腺发育中的作用。通过免疫组织化学分析来研究导管发育和蛋白质表达模式的变化。本研究发现,KO 小鼠在青春期早期的导管发育增加,表现在 6 周时导管面积和终末芽数量增加。此外,KO 小鼠在 4 周时显示出各种蛋白质(Stat1、Fak、Akt、Slug/Snail 和孕激素受体)的表达增加,而与野生型小鼠相比,KO 小鼠从 6 周开始的表达水平降低。这项研究确定了 CSMD1 在乳腺发育中的新作用,CSMD1 KO 导致乳腺发育明显加快,提示乳腺更早形成成人形态。