title: Protein arginine (N)-methyl transferase 7 (PRMT7) as a potential target for the sensitization of tumor cells to camptothecins.
abstract: PRMT7 belongs to the protein arginine methyl-transferases family. We show that downregulation of PRMT7alpha and beta isoforms in DC-3F hamster cells was associated with increased sensitivity to the Top1 inhibitor camptothecin (CPT). This effect was not due to a change in Top1 contents or catalytic activity, or to a difference in the reversal of DNA breaks. Overexpression of PRMT7alpha and beta in DC-3F cells had no effect on CPT sensitivity, whereas it conferred a resistance to DC-3F/9-OH-E cells for which both isoforms are reduced by two- to three-fold as compared to DC-3F parental cells. Finally, downregulation of the human PRMT7 could also sensitize HeLa cells to CPT, suggesting that it could be used as a target to potentiate CPT derivatives.
authors.affiliation: INSERM U916, VINCO, Institut Bergonié and Université Victor Segalen Bordeaux 2, 33076 Bordeaux, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Verbiest
authors.forename: Danièle
authors.initials: D
authors.lastname: Montaudon
authors.forename: Michel T
authors.initials: MT
authors.lastname: Tautu
authors.forename: Joyce
authors.initials: J
authors.lastname: Moukarzel
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Portail
authors.forename: Judith
authors.initials: J
authors.lastname: Markovits
authors.forename: Jacques
authors.initials: J
authors.lastname: Robert
authors.forename: François
authors.initials: F
authors.lastname: Ichas
authors.forename: Philippe
authors.initials: P
authors.lastname: Pourquier
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002166:Camptothecin / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006224:Cricetinae; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008780:Methyltransferases / Q000235:genetics* / Q000378:metabolism; D009369:Neoplasms / Q000201:enzymology*; D016376:Oligonucleotides, Antisense / Q000235:genetics; D011484:Protein-Arginine N-Methyltransferases
chemical_list: D000970:Antineoplastic Agents; D007527:Isoenzymes; D016376:Oligonucleotides, Antisense; D008780:Methyltransferases; C487994:PRMT7 protein, human; D011484:Protein-Arginine N-Methyltransferases; D002166:Camptothecin