BACKGROUND: Recent evidence has implicated the MAP kinase pathway with the development of androgen insensitive prostate cancer (AIPC). We have previously reported gene amplification of critical members of this pathway with the development of androgen insensitive disease. METHODS: Protein expression of Raf-1 was analyzed using immunohistochemistry (IHC) in a database of 65 paired tumor specimens obtained before and after the development of AIPC and correlated with other members of the pathway. RESULTS: Patients whose Raf-1 expression rose with development of AIPC had a significantly shorter median time to biochemical relapse compared to those whose expression fell or remained unchanged (1.16 vs. 2.62 years, P = 0.0005). In AIPC tumors, expression of Raf-1 correlated significantly with expression of HER2 and with expression of c-fos. CONCLUSIONS: We conclude that the HER2/Raf-1/AP-1 axis may promote the development of AIPC, leading to early relapse. Members of the pathway may act as novel therapeutic targets for patients.
BACKGROUND: Recent evidence has implicated the MAP kinase pathway with the development of androgen insensitive prostate cancer (AIPC). We have previously reported gene amplification of critical members of this pathway with the development of androgen insensitive disease. METHODS: Protein expression of Raf-1 was analyzed using immunohistochemistry (IHC) in a database of 65 paired tumor specimens obtained before and after the development of AIPC and correlated with other members of the pathway. RESULTS:Patients whose Raf-1 expression rose with development of AIPC had a significantly shorter median time to biochemical relapse compared to those whose expression fell or remained unchanged (1.16 vs. 2.62 years, P = 0.0005). In AIPC tumors, expression of Raf-1 correlated significantly with expression of HER2 and with expression of c-fos. CONCLUSIONS: We conclude that the HER2/Raf-1/AP-1 axis may promote the development of AIPC, leading to early relapse. Members of the pathway may act as novel therapeutic targets for patients.
Authors: Hui Gao; Xuesong Ouyang; Whitney A Banach-Petrosky; William L Gerald; Michael M Shen; Cory Abate-Shen Journal: Proc Natl Acad Sci U S A Date: 2006-09-14 Impact factor: 11.205
Authors: James A McCubrey; Melissa L Sokolosky; Brian D Lehmann; Jackson R Taylor; Patrick M Navolanic; William H Chappell; Stephen L Abrams; Kristin M Stadelman; Ellis W T Wong; Negin Misaghian; Stefan Horn; Jörg Bäsecke; Massimo Libra; Franca Stivala; Giovanni Ligresti; Agostino Tafuri; Michele Milella; Marek Zarzycki; Andrzej Dzugaj; Francesca Chiarini; Camilla Evangelisti; Alberto M Martelli; David M Terrian; Richard A Franklin; Linda S Steelman Journal: Adv Enzyme Regul Date: 2008-02-21
Authors: James A McCubrey; Linda S Steelman; William H Chappell; Stephen L Abrams; Ellis W T Wong; Fumin Chang; Brian Lehmann; David M Terrian; Michele Milella; Agostino Tafuri; Franca Stivala; Massimo Libra; Jorg Basecke; Camilla Evangelisti; Alberto M Martelli; Richard A Franklin Journal: Biochim Biophys Acta Date: 2006-10-07
Authors: Lucia B Jilaveanu; Christopher R Zito; Saadia A Aziz; Patricia J Conrad; John C Schmitz; Mario Sznol; Robert L Camp; David L Rimm; Harriet M Kluger Journal: Clin Cancer Res Date: 2009-09-08 Impact factor: 13.801