title: Ras oncogene-induced sensitization to 1-beta-D-arabinofuranosylcytosine.
abstract: Human tumor cells containing ras oncogenes display enhanced sensitivity to 1-beta-D-arabinofuranosylcytosine (Ara-C) and other deoxycytidine analogues (H-M. Koo, et al., Cancer Res., 56: 5211-5216, 1996). Human tumor cell lines with or without a ras oncogene as well as a pair of isogenic cell lines with one containing an activated ras oncogene were used to study the basis for differential sensitivity. We found that human tumor cells containing ras oncogenes upon entry into the S phase of the cell cycle underwent apoptosis in response to Ara-C treatment. By contrast, human tumor cells harboring wild-type ras alleles were only delayed in the S phase when exposed to Ara-C. Thus, the ras oncogene specifically renders human cells more sensitive to Ara-C by preventing S-phase arrest. This may occur by the ras oncogene compromising an S-phase checkpoint.
authors.affiliation: Advanced Bioscience Laboratories Basic Research Program, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702, USA.
authors.forename: H M
authors.initials: HM
authors.lastname: Koo
authors.forename: M J
authors.initials: MJ
authors.lastname: McWilliams
authors.forename: W G
authors.initials: WG
authors.lastname: Alvord
authors.forename: G F
authors.initials: GF
authors.lastname: Vande Woude
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis; D002471:Cell Transformation, Neoplastic; D003561:Cytarabine / Q000378:metabolism / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D003842:Deoxycytidine Kinase / Q000096:biosynthesis; D004354:Drug Screening Assays, Antitumor; D011905:Genes, ras / Q000502:physiology*; D006801:Humans; D016196:S Phase; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D000964:Antimetabolites, Antineoplastic; D003561:Cytarabine; D004247:DNA; D003842:Deoxycytidine Kinase