La GTPasa Rac1 como modulador del desarrollo del adenocarcinoma colorrectal humano y como potencial diana terapéutica en cáncer

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dc.contributor.advisor Lacal Sanjuán, Juan Carlos (dir.) es Espina García, Carolina es
dc.contributor.other UAM. Departamento de Biología Molecular es_ES
dc.contributor.other Instituto de Investigaciones Biomédicas “Alberto Sols” (IIB-CSIC-UAM) es 2016-02-18T09:42:46Z 2016-02-18T09:42:46Z 2007-09-11
dc.identifier.uri en
dc.description Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura 11-09-2007 es_ES
dc.description.abstract Colorectal adenocarcinoma is the second cause of cancer mortality in developed countries, and its incidence is increasing in the rest of the world. It results from the progressive accumulation of genetic and epigenetic alterations that lead to the transformation of non-neoplastic colonic epithelial cells into adenoma and, later, adenocarcinoma cells. Appropriate animal models are required to investigate the molecular mechanisms involved in tumor onset and progression of human tumors. Here, a direct orthotopic cell microinjection procedure was evaluated to generate models in which the dissemination pattern closely replicates all relevant tumor sites observed in humans. The injection of human colorectal cancer cell lines between the mucosa and the muscularis externa layers of the cecal wall of athymic mice mimics the human colorectal adenocarcinoma. Rac1 is a member of the Rho family of small guanosine triphosphatases (GTPases) that regulates many intracellular signalling pathways such as adhesion, motility, cell cycle, apoptosis, transcriptional regulation, and membrane trafficking. Their ability to act as general modulators of several cellular processes results in important roles in tumor biology, including tumorigenesis, invasion and metastasis. The role of Rac1 in colorectal tumor growth and progression was investigated by genetic modification of a human colorectal adenocarcinoma cell line to over-express or lack Rac1 expression. shRNA technology was used to block Rac1 mRNA and protein expression. Tumor behavior was studied by orthotopic microinjection of the stably modified cell lines generated. Specific inhibition of Rac1 completely suppressed tumor formation, while over-expression of Rac1 resulted in an accelerated tumorigenic process, inducing a faster mortality rate. To better understand the molecular mechanisms by which Rac1 accelerates tumor progression, attempts were made to define the gene expression profiles of tumor xenografts from cells over-expressing Rac1. The results suggest that Rac1 and its downstream pathways play a major role in colorectal adenocarcinoma progression. Therefore, inhibition of Rac1 function may provide an important tool to interfere with the malignant phenotype of colorectal adenocarcinoma cells and could be used as a novel drug target for cancer therapy. en
dc.format.extent 143 pag. es_ES
dc.format.mimetype application/pdf en
dc.language.iso spa en
dc.subject.other Proteína activante la GTPasa-Tesis doctorales es_ES
dc.subject.other Colon-Cáncer-Tesis doctorales es_ES
dc.title La GTPasa Rac1 como modulador del desarrollo del adenocarcinoma colorrectal humano y como potencial diana terapéutica en cáncer es_ES
dc.type doctoralThesis en
dc.subject.eciencia Biología y Biomedicina / Biología es_ES
dc.rights.accessRights closedAccess en

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