46 research outputs found
The Cytoplasmic Domain of MUC1 Induces Hyperplasia in the Mammary Gland and Correlates with Nuclear Accumulation of β-Catenin
MUC1 is an oncoprotein that is overexpressed in up to 90% of breast carcinomas. A previous in vitro study by our group demonstrated that the cytoplasmic domain of MUC1 (MUC1-CD), the minimal functional unit of MUC1, contributes to the malignant phenotype in cells by binding directly to β-catenin and protecting β-catenin from GSK3β-induced degradation. To understand the in vivo role of MUC1-CD in breast development, we generated a MUC1-CD transgenic mouse model under the control of the MMTV promoter in a C57BL/6J background, which is more resistant to breast tumor. We show that the expression of MUC1-CD in luminal epithelial cells of the mammary gland induced a hyperplasia phenotype characterized by the development of hyper-branching and extensive lobuloalveoli in transgenic mice. In addition to this hyperplasia, there was a marked increase in cellular proliferation in the mouse mammary gland. We further show that MUC1-CD induces nuclear localization of β-catenin, which is associated with a significant increase of β-catenin activity, as shown by the elevated expression of cyclin D1 and c-Myc in MMTV-MUC1-CD mice. Consistent with this finding, we observed that overexpression of MUC1-C is associated with β-catenin nuclear localization in tumor tissues and increased expression of Cyclin D1 and c-Myc in breast carcinoma specimens. Collectively, our data indicate a critical role for MUC1-CD in the development of mammary gland preneoplasia and tumorigenesis, suggesting MUC1-CD as a potential target for the diagnosis and chemoprevention of human breast cancer
Key signaling nodes in mammary gland development and cancer: β-catenin
β-Catenin plays important roles in mammary development and tumorigenesis through its functions in cell adhesion, signal transduction and regulation of cell-context-specific gene expression. Studies in mice have highlighted the critical role of β-catenin signaling for stem cell biology at multiple stages of mammary development. Deregulated β-catenin signaling disturbs stem and progenitor cell dynamics and induces mammary tumors in mice. Recent data showing deregulated β-catenin signaling in metaplastic and basal-type tumors suggest a similar link to reactivated developmental pathways and human breast cancer. The present review will discuss β-catenin as a central transducer of numerous signaling pathways and its role in mammary development and breast cancer
Hybrid III-V/IV Nanowires: High-Quality Ge Shell Epitaxy on GaAs Cores
The integration of optically active III–V and electronic-suitable IV materials on the same nanowire could provide a great potential for the combination of photonics and electronics in the nanoscale. In this Letter, we demonstrate the growth of GaAs/Ge core–shell nanowires on Si substrates by molecular beam epitaxy and investigate the radial and axial Ge epitaxy on GaAs nanowires in detail. High-quality core–shell nanowires with smooth side facets and dislocation-free, sharp interfaces are achieved. It is found that the low shell growth temperature leads to smoother side facets, while higher shell growth temperatures lead to more relaxed structures with significantly faceted sidewalls. The possibility of forming a III–V/IV heterostructure nanowire with a Ge section development in the axial direction of a GaAs nanowire using a Ga droplet is also revealed. These nanowires provide an ideal platform for nanoscale III–V/IV combination, which is promising for highly integrated photonic and electronic hybrid devices on a single chip
Growth and Fabrication of High-Quality Single Nanowire Devices with Radial p-i-n Junctions
Nanowires (NWs) with radial p-i-n junction have advantages, such as large junction area and small influence from the surface states, which can lead to highly efficient material use and good device quantum efficiency. However, it is difficult to make high-quality core–shell NW devices, especially single NW devices. Here, the key factors during the growth and fabrication process that influence the quality of single core–shell p-i-n NW devices are studied using GaAs(P) NW photovoltaics as an example. By p-doping and annealing, good ohmic contact is achieved on NWs with a diameter as small as 50–60 nm. Single NW photovoltaics are subsequently developed and a record fill factor of 80.5% is shown. These results bring valuable information for making single NW devices, which can further benefit the development of high-density integration circuits