Background: Down syndrome (DS), caused by trisomy of human chromosome 21 (HSA21), is the most common genetic birth defect. Congenital heart defects (CHD) are seen in 40% of DS children, and >50% of all atrioventricular canal defects in infancy are caused by trisomy 21, but the causative genes remain unknown.
Results: Here we show that aberrant adhesion and proliferation of DS cells can be reproduced using a transchromosomic model of DS (mouse fibroblasts bearing supernumerary HSA21). We also demonstrate a deacrease of cell migration in transchromosomic cells independently of their adhesion properties. We show that cell-autonomous proteome response to the presence of Collagen VI in extracellular matrix is strongly affected by trisomy 21.
Conclusion: This set of experiments establishes a new model system for genetic dissection of the specific HSA21 gene-overdose contributions to aberrant cell migration, adhesion, proliferation and specific proteome response to collagen VI, cellular phenotypes linked to the pathogenesis of CHD.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2745369 | PMC |
| http://dx.doi.org/10.1186/1477-5956-7-31 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Proteomic analysis of Trichoderma harzianum secretome and their role in the biosynthesis of zinc/iron oxide nanoparticles.
Sci Rep
January 2025
Instituto de Investigaciones en Biodiversidad y Biotecnología (INBIOTEC-CONICET), Fundación para Investigaciones Biológicas Aplicadas (FIBA), Mar del Plata, 7600, Argentina.
The fungal green synthesis of nanoparticles (NPs) has gained great interest since it is a cost-effective and easy handling method. The process is simple because fungi secrete metabolites and proteins capable of reducing metal salts in aqueous solution, however the mechanism remains largely unknown. The aim of this study was to analyze the secretome of a Trichoderma harzianum strain during the mycobiosynthesis process of zinc and iron nanoparticles.
View Article and Find Full Text PDFProteomic profiling identifies upregulation of aurora kinases causing resistance to taxane-type chemotherapy in triple negative breast cancer.
Sci Rep
January 2025
Department of Genetics, The University of Alabama at Birmingham, Birmingham, AL, USA.
Nowadays, chemotherapy and immunotherapy remain the major treatment strategies for Triple-Negative Breast Cancer (TNBC). Identifying biomarkers to pre-select and subclassify TNBC patients with distinct chemotherapy responses is essential. In the current study, we performed an unbiased Reverse Phase Protein Array (RPPA) on TNBC cells treated with chemotherapy compounds and found a leading significant increase of phosphor-AURKA/B/C, AURKA, AURKB, and PLK1, which fall into the mitotic kinase group.
View Article and Find Full Text PDFHistopathology and proteomics are synergistic for high-grade serous ovarian cancer platinum response prediction.
NPJ Precis Oncol
January 2025
Eötvös Loránd University, Department of Physics of Complex Systems, Budapest, Hungary.
Patients with High-Grade Serous Ovarian Cancer (HGSOC) exhibit varied responses to treatment, with 20-30% showing de novo resistance to platinum-based chemotherapy. While hematoxylin-eosin (H&E)-stained pathological slides are used for routine diagnosis of cancer type, they may also contain diagnostically useful information about treatment response. Our study demonstrates that combining H&E-stained whole slide images (WSIs) with proteomic signatures using a multimodal deep learning framework significantly improves the prediction of platinum response in both discovery and validation cohorts.
View Article and Find Full Text PDFLongitudinal omics data and preclinical treatment suggest the proteasome inhibitor carfilzomib as therapy for ibrutinib-resistant CLL.
Nat Commun
January 2025
Division of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Chronic lymphocytic leukemia is a malignant lymphoproliferative disorder for which primary or acquired drug resistance represents a major challenge. To investigate the underlying molecular mechanisms, we generate a mouse model of ibrutinib resistance, in which, after initial treatment response, relapse under therapy occurrs with an aggressive outgrowth of malignant cells, resembling observations in patients. A comparative analysis of exome, transcriptome and proteome of sorted leukemic murine cells during treatment and after relapse suggests alterations in the proteasome activity as a driver of ibrutinib resistance.
View Article and Find Full Text PDF(P)ppGpp synthetase Rel facilitates cellulose formation of biofilm by regulating glycosyltransferase in Brucella abortus.
Int J Biol Macromol
January 2025
College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, China; Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, Northwest A&F University; Yangling, Shaanxi 712100, China. Electronic address:
Biofilms are complex adhesive structures that establish chronic infection and allow robust protection from external stressors such as antibiotics. Cellulose as one of the compositions of bacteria biofilm which protect bacteria from stress, host immune responses and resistance to antibiotics. Bacterial stress responses are regulated via guanosine pentaphosphate and tetraphosphate (p)ppGpp.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!