A5036887524- Cancer-related Molecular Pathways
- Chronic Myeloid Leukemia Treatments
- Chronic Lymphocytic Leukemia Research
- Cell death mechanisms and regulation
- Ubiquitin and proteasome pathways
- Acute Myeloid Leukemia Research
- Cancer, Lipids, and Metabolism
- Protein Kinase Regulation and GTPase Signaling
- Cancer Mechanisms and Therapy
- Genomics and Chromatin Dynamics
- PI3K/AKT/mTOR signaling in cancer
- Protein Degradation and Inhibitors
- Epigenetics and DNA Methylation
- Lymphoma Diagnosis and Treatment
- Eosinophilic Disorders and Syndromes
- Retinoids in leukemia and cellular processes
- Antibiotic Resistance in Bacteria
- Melanoma and MAPK Pathways
- Cancer-related gene regulation
- Histone Deacetylase Inhibitors Research
- NF-κB Signaling Pathways
- Peptidase Inhibition and Analysis
- Signaling Pathways in Disease
- Microtubule and mitosis dynamics
- Immune Cell Function and Interaction
Universidad de Cantabria
2015-2024
Instituto de Biomedicina y Biotecnología de Cantabria
2015-2024
Consejo Superior de Investigaciones Científicas
2000-2023
Copenhagen University Hospital
2018
Hospital Braga
2018
Marqués de Valdecilla University Hospital
1995-2011
Centro de Investigación Biomédica en Red
2011
Hospital Universitario de Gran Canaria Doctor Negrín
2004
Centro de Investigaciones Biológicas Margarita Salas
1999-2000
Unidades Centrales Científico-Técnicas
2000
Hematopoiesis is a process capable of generating millions cells every second, as distributed in many cell types. The regulated by number transcription factors that regulate the differentiation along distinct lineages and dictate genetic program defines each mature phenotype. Myc was first discovered oncogene avian leukemogenic retroviruses; it later found translocated human lymphoma. From then on, evidence accumulated showing c-Myc one playing major role hematopoiesis. study genetically...
We compared the expression of ras gene family (H-ras, K-ras, and N-ras) in adult mouse tissues during development. found substantial variations among different organs amounts transcripts originating from each gene, especially for N-ras gene. The patterns were consistent with reported preferential tissue activation genes suggested cellular functions genes.
SKP2 is the ubiquitin ligase subunit that targets p27(KIP1) (p27) for degradation. induced in G(1)-S transit of cell cycle, frequently overexpressed human cancer, and displays transformation activity experimental models. Here we show MYC induces expression at mRNA protein levels myeloid leukemia K562 cells with conditional expression. Importantly, these systems, induction did not activate proliferation, ruling out up-regulation as a consequence cycle entry. MYC-dependent was also detected...
Abstract Cell cycle stimulation is a major transforming mechanism of Myc oncoprotein. This achieved through at least three concomitant mechanisms: upregulation cyclins and Cdks, downregulation the Cdk inhibitors p15 p21 degradation p27. The Myc-p27 antagonism has been shown to be relevant in human cancer. To degraded, p27 must phosphorylated Thr-187 recognized by Skp2, component ubiquitination complex. We previously described that induces Skp2 expression. Here we show not only Cdk2 but Cdk1...
CTCF is a widely expressed and highly conserved multi-Zn-finger (ZF) nuclear factor. Binding to various target sites (CTSs) mediated by combinatorial contributions of different ZFs. Different CTSs mediate distinct functions in transcriptional regulation, including promoter repression or activation hormone-responsive gene silencing. In addition, the necessary sufficient core sequences diverse enhancer-blocking (insulator) elements, CpG methylation-sensitive ones, have recently been pinpointed...
In vitro DNA amplification followed by oligonucleotide mismatch hybridization was used to study the frequency of HRAS mutations in benign self-regressing skin tumors keratoacanthomas and squamous cell carcinomas. We freshly obtained as well Formalin-fixed paraffin-embedded tissues from both types tumors. 50 samples each tumor type analyzed for activating involving codons 12 61. A relatively high percentage (30%) found compared with 13% The most frequent mutation identified is A-T-to-T.A...
Abstract Untreated chronic myeloid leukemia (CML) progresses from phase to blastic crisis (BC). Increased genomic instability, deregulated proliferation, and loss of differentiation appear associated BC, but the molecular alterations underlying progression CML are poorly characterized. MYC oncogene is frequently in human cancer, often with tumor progression. Genomic instability induction aberrant DNA replication described as effects MYC. In this report, we studied activities cell lines...
The cyclin-dependent kinase (Cdk) inhibitors p21(Cip1) and p27(Kip1) have been proposed to exert redundant functions in cell cycle progression differentiation programs, although nonoverlapping also described. To gain further insights into the relevant mechanisms detect possible functional differences between both proteins, we conditionally expressed K562, a multipotent human leukemia line. Temporal ectopic expression of either or arrested proliferation, inhibited Cdk2 Cdk4 activities,...
Multiple functions have been reported for the transcription factor and candidate tumour suppressor, CTCF. Among others, they include regulation of cell growth, differentiation apoptosis, enhancer-blocking activity control imprinted genes. CTCF is usually localized in nucleus its subcellular distribution during cycle dynamic; was found associated with mitotic chromosomes midbody, suggesting different roles at stages cycle. Here we report nucleolar localization several experimental model...
The involvement of the ras oncogenes in tumorigenesis was investigated keratoacanthomas, which are benign and self-regressing skin tumors, both humans a corresponding animal model system. Keratoacanthomas were induced on rabbit ears by repeated applications 7,12-dimethylbenz(a)anthracene. About 60% tumor DNAs produced transformed foci after transfection into NIH 3T3 cells, all them transforming gene identified as H-ras Southern Northern (RNA) hybridization. Immunoprecipitation experiments...
Despite its early discovery and relevance in cancer, the mechanisms by which MYC brings about tumorigenic transformation have not been clarified. elicits a variety of biological activities, proliferation promotion being best studied. However, inhibition cell differentiation was one first activities described. The importance impairment MYC-induced tumorigenesis is demonstrated transgenic mice models with conditional expression, where inactivation leads to tumor regression associated...
It has been previously described that p21 functions not only as a CDK inhibitor but also transcriptional co-repressor in some systems. To investigate the roles of control, we studied gene expression changes two human cell Using leukemia line (K562) with inducible and primary keratinocytes adenoviral-mediated expression, carried out microarray-based profiling. We found rapidly strongly repressed mRNA levels number genes involved cycle mitosis. One most down-regulated was CCNE2 (cyclin E2...
The transcription factor MYC regulates cell proliferation, transformation, and survival in response to growth signaling that is mediated part by the kinase activity of ERK2. Because ERK2 can also bind DNA modify gene expression, we investigated whether it more directly transcription. We identified binding sites promoter detected at various serum-stimulated types. Expression nuclear-localized constructs serum-starved cells revealed nucleus—regardless its activity—increased mRNA expression...
CTCF is a transcription factor and candidate tumor suppressor that contains DNA-binding domain composed of 11 zinc fingers. We reported previously differentially regulated during differentiation human myeloid leukemia cells. In this study we aimed to investigate the role in cell differentiation. A line, K562, can be chemically induced differentiate into various hematopoietic lineages was chosen as model system for study. Several K562 lines with constitutive conditional expression have been...