Item type:Thesis, Open Access

Chemo- und Radioresistenzverhalten kleinzelliger Bronchialkarzinomzellinien in Adhärenz- und Suspensionskultur

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Date

2005-07-28

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Philipps-Universität Marburg
DOI

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Abstract

Most small cell lung cancer (SCLC) patients relapse within 12 months of starting combination chemotherapy plus radio-therapy, due to the development of acquired chemo- and radio-resistance. This phenomenon relates to the induction of tumour differentiation, resulting in apoptosis-resistant, morphologically variant (v-SCLC) cells, which lack the neuroendocrine expression of classic (c-) SCLC cells. In this study spontaneously adherent SCLC sublines were shown by differential gene expression analysis to provide an in vitro model of variant differentiation in SCLC, with down-regulation of neuroendocrine markers and up-regulation of epithelial differentiation markers. The sensitivity of adherent SCLC sublines to etoposide, cyclophosphamide and gamma radiation was significantly diminished relative to parent suspension cell lines. Western blot analysis using phosphorylation-specific antibodies to Akt and MAP kinase revealed markedly elevated activation in adherent SCLC sublines, paralleled by increased levels of phosphorylated Bad protein and activated NF-kappaB. Subcultivation of the adherent sublines on uncoated surfaces reversed their adherent phenotype immediately and under these conditions Akt activity reverted to low levels. These results suggest that c-SCLC cells can differentiate spontaneously to v-SCLC and that the associated cellular adhesion may trigger Akt-dependent inhibition of apoptosis in SCLC cells, thus leading to acquired chemo- and radio-resistance.

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Dates
Created: 2005Issued: 2005-07-28Updated: 2011-08-10
DOI
https://doi.org/10.17192/z2005.0384
Faculty
Medizin
Publisher
Philipps-Universität Marburg
Language
ger
Data types
DoctoralThesis
Keywords
ChemoresistanceAdhäsionApoptosisApoptoseAdhesionRadioresistanceChemoresistenzBronchialkarzinomStrahlenresistenzSCLC
DFG-subjects
Arzneimittelresistenz
DDC-Numbers
610
License
https://rightsstatements.org/vocab/InC-NC/1.0/
URI
https://open.uni-marburg.de/handle/10.17192/z2005.0384
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Bachmann, Sven-Oliver (130262935): Chemo- und Radioresistenzverhalten kleinzelliger Bronchialkarzinomzellinien in Adhärenz- und Suspensionskultur. : Philipps-Universität Marburg 2005-07-28. DOI: https://doi.org/10.17192/z2005.0384.

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