Protein arginine (N)-methyl transferase 7 (PRMT7) as a potential target for the sensitization of tumor cells to camptothecins.
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.
Verbiest
Vincent
V
INSERM U916, VINCO, Institut Bergonié and Université Victor Segalen Bordeaux 2, 33076 Bordeaux, France.
Montaudon
Danièle
D
Tautu
Michel T
MT
Moukarzel
Joyce
J
Portail
Jean-Pierre
JP
Markovits
Judith
J
Robert
Jacques
J
Ichas
François
F
Pourquier
Philippe
P
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
D000970:Antineoplastic Agents; D007527:Isoenzymes; D016376:Oligonucleotides, Antisense; D008780:Methyltransferases; C487994:PRMT7 protein, human; D011484:Protein-Arginine N-Methyltransferases; D002166:Camptothecin