Human Gene Set: CALVET_IRINOTECAN_SENSITIVE_VS_REVERTED_UP


Standard name CALVET_IRINOTECAN_SENSITIVE_VS_REVERTED_UP
Systematic name M1750
Brief description Genes up-regulated in neuroblastoma xenografts: resistant vs those that reverted to be sensitive to the topoisomerase inhibitor irinotecan [PubChem=3750].
Full description or abstract In vivo neuroblastoma (NB) xenograft model, resistant to the DNA-topoisomerase I inhibitor irinotecan (CPT-11), has been established to study resistance mechanisms acquired in a therapeutic setting. Common mechanisms of resistance were not involved in this resistance. Thus, we compared the gene expression profiles of sensitive, resistant, and reverted tumors using cDNA expression arrays. Expression of selected transcripts was confirmed by quantitative real-time PCR. We found that pleiotrophin (PTN), a heparin-binding growth factor, was the only gene significantly affected: PTN gene expression was downregulated in all resistant tumors (8-14-fold) as compared to sensitive tumors, and was increased (2-4-fold) in all reverted tumors as compared to resistant tumors. PTN thus appeared to be a likely candidate gene associated with resistance to CPT-11 in this in vivo model. To investigate the direct implication of PTN in NB, we transfected two NB cell lines with RNA interferences in order to silence PTN. PTN failed to demonstrate implication in resistance to CPT-11 in vitro but could influence sensitivity to CPT-11 exclusively through an in vivo mechanism. Indeed, vasculature was significantly enhanced in resistant NB xenografts compared to sensitive and reverted xenografts, and we suggest that PTN is acting in our resistant in vivo NB model as an angiostatic factor.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 16501609   Authors: Calvet L,Geoerger B,Regairaz M,Opolon P,Machet L,Morizet J,Joseph JM,Elie N,Vassal G
Exact source Table 1: resistant vs reverted
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Source species Homo sapiens
Contributed by Arthur Liberzon (MSigDB Team)
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identifier namespace		 HUMAN_SEQ_ACCESSION
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