Untersuchungen zu Regulationsmechanismen von Hypoxie-induzierbaren-Faktoren und deren Zielgenen in den Tumorzelllinien H23, A549 und H69

Die Karzinogenese ist ein multi-komplexer Prozess, der durch DNA-Schädigung bzw. Mutation, Überexpression von Onkogenen und / oder Funktionsverlust von Tumorsuppressorgenen zu einer dysregulierten Zellproliferation führt. Aus dieser schnellen, dysregulierten Proliferation des Tumorgewebes resultiert...

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Bibliographic Details
Main Author: Mahlik, Pierre Pasqual
Contributors: Rose, Frank (Prof. Dr.) (Thesis advisor)
Format: Doctoral Thesis
Published: Philipps-Universität Marburg 2009
Online Access:PDF Full Text
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Carcinogenesis is a complex process leading to abnormal regulation of cell proliferation through DNA-damage and respectively -mutation, overexpression of oncogenes and/ or loss of function of tumor suppressor genes. As a result tumor-hypoxia evolves from a fast and impaired proliferation of tumor tissue. It is an established fact that tumors are only fed through diffusion up to a size of 100-200 µm, which reveals that growth of solid tumors depends on sufficient angiogenesis. The hypoxia-inducible-factor 1 (HIF-1), a hetero-dimer, consisting of two subunits HIF-1α and HIF-1β is induced in low oxygen pressure and mediates activation of target genes for adaption of tumor cells to hypoxia, giving HIF-1 a key role in tumor progression. The background of this dissertation was the characterization of hypoxic effects in human pulmonal tumor cell lines A549, H23 (NSCLC) and H69 (SCLC) regarding the transcription factors HIF-1a , HIF-2a and HIF-3a and its target genes of angiogenesis (VEGF), glycolysis (PGK) and apoptosis. This data resulted in further studies of possible „alternative regulation mechanisms“ of HIF-1a using tumor suppressor gene PTEN and oncogen HER2(neu).