Stairs Douglas B, Notarfrancesco Kathleen L, Chodosh Lewis A
Department of Cancer Biology, Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, 19104-6160, USA.
Transgenic Res. 2005 Dec;14(6):919-40. doi: 10.1007/s11248-005-1806-6.
STK16/Krct (Kinase related to cerevisiae and thaliana) is a ubiquitously expressed member of a unique family of serine/threonine protein kinases that is conserved among all eukaryotes. Despite its cloning 6 years ago to date, the function of this kinase remains unknown. In an attempt to identify a function for Krct, we have generated a doxycycline-dependent transgenic mouse model that permits the inducible overexpression of Krct in the mammary glands of mice treated with tetracycline derivatives. Analysis of these mice reveals that modest overexpression of Krct in the mammary gland during puberty results in duplication of the terminal endbud axis such that multiple, rather than single, budding structures arise at the ends of primary ducts. Supernumerary endbuds in Krct overexpressing mice resemble wild-type terminal endbuds with regard to cellular proliferation rates and localization of cap cells, myoepithelial cells and body cells. However, aberrant transgenic endbuds are surrounded by an increased amount of periductal stroma that in many cases encompasses the entire endbud. These data suggest that Krct may play a role in regulating stromal-epithelial interactions that occur during ductal morphogenesis in the mammary gland.
STK16/Krct(与酿酒酵母和拟南芥相关的激酶)是丝氨酸/苏氨酸蛋白激酶独特家族中普遍表达的成员,在所有真核生物中保守。尽管该激酶在6年前就已克隆,但至今其功能仍不清楚。为了确定Krct的功能,我们构建了一种依赖强力霉素的转基因小鼠模型,该模型允许在用四环素衍生物处理的小鼠乳腺中诱导性过表达Krct。对这些小鼠的分析表明,青春期乳腺中适度过表达Krct会导致末端终末芽轴重复,使得在初级导管末端出现多个而非单个的芽状结构。过表达Krct的小鼠中的额外终末芽在细胞增殖率以及帽细胞、肌上皮细胞和体细胞的定位方面类似于野生型末端终末芽。然而,异常的转基因终末芽被增加的导管周围基质所包围,在许多情况下整个终末芽都被包围。这些数据表明,Krct可能在调节乳腺导管形态发生过程中发生的基质 - 上皮相互作用中发挥作用。