HER2 is a tyrosine kinase receptor causally involved in cancer. A subgroup of breast cancer patients with particularly poor clinical outcome expresses a heterogeneous collection of HER2 carboxy-terminal fragments (CTFs). However, since the CTFs lack the extracellular domain that drives dimerization and subsequent activation of full-length HER2, they are in principle expected to be inactive. Here we present evidence that at low expression levels one of these fragments, 611-CTF, activated multiple signaling pathways because of its unanticipated ability to constitutively homodimerize. A transcriptomic analysis revealed that 611-CTF specifically controlled the expression of genes that we found correlated with poor prognosis in breast cancer. Among the 611-CTF-regulated genes were several that previously have been linked to metastasis, including MET, EPHA2, MMP1, IL11, ANGPTL4 and different Integrins. Transgenic mice overexpressing HER2 in the mammary gland develop tumors only after acquisition of activating mutations in the transgene. In contrast, we show that expression of 611-CTF led to development of aggressive and invasive mammary tumors without the need for mutations. These results demonstrate that 611-CTF is a potent oncogene capable of promoting mammary tumor progression and metastasis.
A naturally occurring HER2 carboxy-terminal fragment promotes mammary tumor growth and metastasis.
Cell line, Time
View SamplesEvaluation of early transcriptional changes in blood brain barrier genes involved in the patogenesis of brain edema associated with ALF.
No associated publication
Specimen part
View SamplesIdentify differentially expressed genes related to the neurodegenerative process in a new animal model of hepatic encephalopathy (HE).
Cerebellar neurodegeneration in a new rat model of episodic hepatic encephalopathy.
Specimen part, Treatment
View SamplesDiabetic retinopathy is one of the leading causes of blindness in diabetic patients. Emerging evidence suggests that retinal neurodegeneration is an early event in the pathogenesis of diabetic retinopathy, but the underlying causes of neuronal loss are unknown.
The db/db mouse: a useful model for the study of diabetic retinal neurodegeneration.
Specimen part
View SamplesNeuroblastoma (NB) is a neoplasm of the sympathetic nervous system, and is the most common solid tumor of infancy. NBs are very heterogeneous, with a clinical course ranging from spontaneous regression to resistance to all current forms of treatment. High-risk patients need intense chemotherapy, and only 30-40% will be cured. Relapsed or metastatic tumors acquire multi-drug resistance, raising the need for alternative treatments. Owing to the diverse mechanisms that are responsible of NB chemoresistance, we aimed to target epigenetic factors that control multiple pathways to bypass therapy resistance. We found that the SWI/SNF-related, matrix-associated, actin- dependent regulator of chromatin, subfamily a, member 4 (SMARCA4/BRG1) was consistently upregulated in advanced stages of NB, with high BRG1 levels being indicative of poor outcome. Loss-of-function experiments in vitro and in vivo showed that BRG1 is essential for the proliferation of NB cells. Furthermore, whole genome transcriptome analysis revealed that BRG1 controls the expression of key elements of oncogenic pathways such as PI3K/AKT and BCL2, which offers a promising new combination therapy for high-risk NB
BRG1/SMARCA4 is essential for neuroblastoma cell viability through modulation of cell death and survival pathways.
Cell line
View SamplesWe sought to find a gene-expression multigene predictor of response to infliximab therapy in Rheumatoid Arthritis patients. Using internal and external cross-validation systems we have built and validated an 8-gene predictor for response to infliximab.
An eight-gene blood expression profile predicts the response to infliximab in rheumatoid arthritis.
Sex, Specimen part, Disease, Disease stage
View SamplesNew and effective therapeutical options are available for the treatment of Rheumatoid Arthritis. One of such treatments is rituximab, and chimeric anti-CD20 antibody that selectively depletes the CD20+ B cell subpopulation.
Identification of candidate genes for rituximab response in rheumatoid arthritis patients by microarray expression profiling in blood cells.
Specimen part, Disease, Disease stage
View SamplesA genetic study of the PRF1 gene has shown association of several polymorphisms with multiple sclerosis (MS). Haplotype analysis identified risk haplotypes strongly associated with male patients having the primary-progressive form of MS (PPMS). Gene expression microarrays were performed in 10 male PPMS patients carrying the risk (n=6) and protective haplotypes (n=4) in order to identify pathways associated with the risk haplotypes. Pathway analysis revealed overrepresentation of the cell killing gene ontology category among down-regulated genes in patients carrying risk haplotypes compared with patients carrying protective haplotypes.
Gender-associated differences of perforin polymorphisms in the susceptibility to multiple sclerosis.
Sex, Specimen part, Disease
View SamplesPermanent synthetic meshes are a prized option to promote soft-tissue support and repair in several surgical procedures. Contrariwise, the risk to develop biomaterial-associated infection (BAI) has not been solved. Intrinsically antibacterial materials, such as those that include metals with antimicrobial activity as part of their composition, are an advanced approach to be further explored for BAI prevention. In this study, a panel of in vitro, ex vivo and in vivo assays was used to compare a novel polypropylene-based surgical mesh modified with silver-containing microparticles with a commercially available similar device normally used for hernia repair. To comprehensively identify specific mechanisms of how the new silver-containing meshes influence the full host-tissue response in the presence and absence of infection, prostheses were screened for cytotoxicity, biological integration and transcriptomic responses, and additional antibiofilm production behaviour. Silver-modified polypropylene meshes exhibited good properties in terms of mechanical and cytotoxic values, as well as a modest prevention of biofilm formation. Moreover, they promoted connective tissue deposition and angiogenesis and, outstandingly, induced immunomodulating effects that may be potentially useful in the clinical context. Overall, the results substantiate the potential use of polypropylene surgical meshes modified with silver-containing microparticles as a means to prevent BAI in soft tissue repair.
No associated publication
Sex, Age, Specimen part
View SamplesGene expression profiles of paired normal adjacent mucosa and tumor samples from 98 individuals and 50 healthy colon mucosae, were obtained through Affymetrix Human Genome U219 Arrays. This dataset is in the context of the COLONOMICS project and to query additional information you can visit the project website www.colonomics.org.
Discovery and validation of new potential biomarkers for early detection of colon cancer.
Sex, Age, Disease, Subject
View Samples