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Lapatinib downregulates fluoropyrimidine-target genes.

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posted on 16.06.2009, 01:29 by Hwang-Phill Kim, Young-Kwang Yoon, Jin-Won Kim, Sae-Won Han, Hyung-Seok Hur, Jinah Park, Ju-Hee Lee, Do-Youn Oh, Seock-Ah Im, Yung-Jue Bang, Tae-You Kim

A, Downregulated fluoropyrimidine-sensitivity genes by oligonucleotide microarray based on analysis comparing DMSO/lapatinib-treatment versus DMSO/gefitinib-treatment samples at 24 hours of each treatment in SNU216, SNU484, or SNU668 cells. B, The indicated cells were treated with lapatinib (0.1, 1, 1 µmol/L) for 24 hours. mRNA levels of E2F1 and TS were assessed via RT-PCR (upper). β-Actin was utilized as a loading control. Western blots are provided for E2F1 and TS (lower). α-tubulin was employed as a loading control. C and D, N87, and SKBr3 cells were grown for 24 hours in the presence of gefitinib (0.01, 0.1, 1 µmol/L) or lapatinib (0.01, 0.1, 1 µmol/L). Western blots are shown for phosphorylated and total EGFR, and HER2. mRNA levels of TS, TK1, DHFR, and RRM2 were determined via quantitative real-time RT-PCR. Columns, means; bars, ±SD. *, P<0.05; **, P<0.05;***, P<0.05, gefitinib versus lapatinib at 0.01, 0.1, and 1 µmol/L doses. The expressed data are representative of three independent experiments.