Prolonged extracellular signal-regulated kinase 1/2 activation during fibroblast growth factor 1- or heregulin beta1-induced antiestrogen-resistant growth of breast cancer cells is resistant to mitogen-activated protein/extracellular regulated kinase kinase inhibitors

Cancer Research
Jaideep V ThottasseryFrancis G Kern

Abstract

Increased growth factor receptor signaling is implicated in antiestrogen-resistant breast tumors suggesting that abrogation of such signaling could restore or prolong sensitivity to antihormonal agents. Activation of the mitogen-activated protein/extracellular regulated kinase kinase (MEK)-extracellular regulated kinase (ERK)1/2 cascade is a common component of such pathways. We investigated the ability of the MEK activation inhibitor U0126 to block the increased growth of estrogen receptor-positive MCF-7 breast cancer cells caused by fibroblast growth factor 1 (FGF-1), heregulin beta1 (HRGbeta1), and epidermal growth factor (EGF) in the presence of the pure antiestrogen ICI 182780 (Faslodex; fulvestrant). We found that either FGF-1 or HRGbeta1 but not EGF substantially reduced the inhibitory effects of U0126 on growth and ERK1/2 activation, including the combined inhibitory effects of U0126 and ICI 182780. FGF-1 and HRGbeta1 also reduced the inhibition of ERK1/2 phosphorylation by the MEK inhibitors PD98059 and PD184161. Interestingly, a transiently transfected dominant-negative MEK1 completely abrogated activation of a coexpressed green fluorescent protein-ERK2 reporter by all three of the factors. Despite a short-lived activ...Continue Reading

References

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Citations

Aug 15, 2012·Proceedings of the National Academy of Sciences of the United States of America·Michio HiroshimaYasushi Sako
Sep 3, 2002·American Journal of Respiratory Cell and Molecular Biology·Jinbo Liu, Jeffrey A Kern
Nov 16, 2007·Molecular Systems Biology·Marc R BirtwistleBoris N Kholodenko
Mar 22, 2015·Pancreatology : Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]·Mircea BeuranSorin Hostiuc
Feb 25, 2015·Pancreatology : Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]·Bo KongJörg Kleeff
Aug 18, 2017·Molecular Pharmacology·Maroua JalouliDarren E Richard
Dec 7, 2007·Cancer Research·Louise WestbrookJaideep V Thottassery
Dec 5, 2006·The Journal of Biological Chemistry·Takeshi NagashimaMariko Hatakeyama
Apr 15, 2018·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Longguang TangXianzhong Zhang

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