title: Genome-wide gene expression analysis of chemoresistant pulmonary carcinoid cells.
abstract: OBJECTIVE
  Carcinoids are highly chemoresistant tumors associated with a dismal prognosis. This study involved a comparison of the genome-wide gene expression pattern of a chemoresistant and a chemosensitive pulmonary carcinoid cell line to reveal factors that contribute to the resistant phenotype.
  
  
  METHODS
  Gene expression of UMC-11 chemoresistant carcinoid cells as assessed by 32 K microarray was compared with H835 chemosensitive carcinoid cells, and the genes that were differentially expressed and expected to be related to chemoresistance were selected.
  
  
  RESULTS
  Drug-resistant UMC-11 cells exhibited increased expression of transcripts known to confer resistance to different cytostatics such as P-glycoprotein, multidrug resistance-associated proteins 2 and 3, effectors of the glutathione detoxification and xenobiotics degradation pathways, and ion transporters including Na+/K+-adenosine triphosphatase. In addition, enhanced transcription of several S100 proteins, capable of suppressing apoptosis, regulation of topoisomerase I (topo I) expression by antisense transcripts fromTOPO1pseudogenes, and alterations of the cytoskeleton seem to contribute to the multidrug-resistant phenotype. A multitude of epidermal growth factor (EGF)-related and neuropeptide growth factors, overexpression of proteases, and appearance of aerobic glycolytic metabolism complement the malignant phenotype of the UMC-11 cells.
  
  
  CONCLUSIONS
  The multidrug-resistant phenotype of the UMC-11 pulmonary carcinoid cell line seems to be mediated by classical efflux pumps, drug metabolization or conjugation systems, and, possibly, modulation of apoptotic cell death by S100 proteins and topo I expression by pseudogene transcripts. Autocrine or paracrine stimulation by a host of EGF-related and neuropeptide growth factors, as well as high metastatic potency indicated by increased expression of components of aerobic glycolysis and proteolytic enzymes, may furthermore account for the failure of therapeutic interventions.
authors.affiliation: Ludwig Boltzmann Cluster of Translational Oncology, Ludwig Boltzmann Society, Vienna, Austria.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Olszewski
authors.affiliation: Ludwig Boltzmann Cluster of Translational Oncology, Ludwig Boltzmann Society, Vienna, Austria.
authors.forename: Robert
authors.initials: R
authors.lastname: Zeillinger
authors.affiliation: Ludwig Boltzmann Cluster of Translational Oncology, Ludwig Boltzmann Society, Vienna, Austria.
authors.forename: Klaus
authors.initials: K
authors.lastname: Geissler
authors.affiliation: Ludwig Boltzmann Cluster of Translational Oncology, Ludwig Boltzmann Society, Vienna, Austria.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Hamilton
keywords: apoptosis; drug resistance; drug transporter; microarray; neuroendocrine tumor