TY - JOUR T1 - A Prenylation Inhibitor (Sodium Phenylacetate) Differently Affects MCF-7 Cell Death when <em>ras</em> is Overexpressed, Partly Involving P42/44, JNK and P38 Kinase Activations JF - Anticancer Research JO - Anticancer Res SP - 1029 LP - 1037 VL - 28 IS - 2A AU - MÉLANIE DI BENEDETTO AU - MICHEL CRÉPIN AU - MICHEL KRAEMER AU - OLIVIER OUDAR Y1 - 2008/03/01 UR - http://ar.iiarjournals.org/content/28/2A/1029.abstract N2 - Background: Sodium phenylacetate (NaPa) inhibits breast cancer cell proliferation decreasing prenylation of small G proteins including Ras. Materials and Methods: Aponecrosis induced by NaPa in MCF-7 and MCF-7ras breast cancer cells was evaluated by measuring Annexin V/PI labelling by flow cytometry. Specific inhibitors of p42/44 (PD 98059), p38 (SB 600125) and JNK (SP 202190) in association with NaPa were also tested. Mitogen-activated kinase (MAPK) activation was measured by immunoprecipitation. Results: NaPa induced cell death more efficiently (80%) in the MCF-7ras cells compared to the MCF-7 cells (60%). NaPa activated ERK 1/2 and its combination with PD 98059 decreased cell death in the MCF-7ras cells in contrast to the MCF-7 cells. Combination of NaPa with specific inhibitors of both JNK and p38 kinases also partly decreased MCF-7ras cell death. Conclusion: NaPa induced cell death differently when ras was overexpressed in breast cancer cells, partly involving p42/44, JNK and p38 pathways. ER -