Distinct Requirements for Adaptor Proteins NCK1 and NCK2 in Mammary Gland Development

AbstractThe adaptor proteins NCK1 and NCK2 are well-established signalling nodes that regulate diverse biological processes including cell proliferation and actin dynamics in many tissue types. Here we have investigated the distribution and function ofNck1 andNck2 in the developing mouse mammary gland. Using publicly available single-cell RNA sequencing data, we uncovered distinct expression profiles between the two paralogs.Nck1 showed widespread expression in luminal, basal, stromal and endothelial cells, whileNck2 was restricted to luminal and basal cells, with prominent enrichment in hormone-sensing luminal subtypes. Next, using mice with global knockout ofNck1 orNck2, we assessed mammary gland development during and after puberty (5, 8 and 12  weeks of age). Mice lackingNck1 orNck2 displayed significant defects in ductal outgrowth and branching at 5  weeks compared to controls, and the defects persisted inNck2 knockout mice at 8  weeks before normalizing at 12 weeks. These defects were accompanied by an increase in epithelial cell proliferation at 5 weeks and a decrease at 8 weeks in bothNck1 andNck2 knockout mice. We also profiled expression of several key genes associated with mammary gland development at these timepoints and detected temporal changes in transcript levels of hormone receptors as well as effectors of cell proliferation and migration inNck1 andNck2 knockout mice, in line with the distinct phenotypes observed at 5 and 8  weeks. Together these studi...
Source: Journal of Mammary Gland Biology and Neoplasia - Category: Cancer & Oncology Source Type: research