title: Epidermal growth factor induces p38 MAPK-dependent G0/G1-to-S transition in prostate cancer cells upon androgen deprivation conditions.
abstract: Epidermal growth factor (EGF) is thought to contribute to the emergence of castration-resistant (CR) prostate tumors by inducing proliferation of cancer cells despite the low levels of circulating androgens achieved by androgen deprivation therapy. We show that, in LNCaP cells, androgen deprivation induces arrest in the G0/G1 cell cycle phase, and that EGF partially rescues this arrest without affecting cell death. Inhibition of p38 MAPK, but not MEK or IKK-β, completely abrogates the EGF-induced proliferation of LNCaP cells in androgen-depleted medium, and decreases the fraction of G0/G1-arrested cells. Our results suggest that EGF enables prostate cancer cells to overcome the growth restriction imposed by androgen deprivation by stimulating G0/G1-to-S transition via p38 MAPK. These results suggest the potential of developing therapies for advanced prostate cancer that block the G0/G1 to S transition, such as by targeting p38 MAPK, or that aim to induce apoptosis in G0/G1-arrested cancer cells.
authors.affiliation: a Department of Biomedicine and Biotechnology , University of Alcalá , Alcalá De Henares, Madrid , Spain.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Rodríguez-Berriguete
authors.affiliation: a Department of Biomedicine and Biotechnology , University of Alcalá , Alcalá De Henares, Madrid , Spain.
authors.forename: Norelia
authors.initials: N
authors.lastname: Torrealba
authors.affiliation: a Department of Biomedicine and Biotechnology , University of Alcalá , Alcalá De Henares, Madrid , Spain.
authors.forename: Benito
authors.initials: B
authors.lastname: Fraile
authors.affiliation: a Department of Biomedicine and Biotechnology , University of Alcalá , Alcalá De Henares, Madrid , Spain.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Paniagua
authors.affiliation: a Department of Biomedicine and Biotechnology , University of Alcalá , Alcalá De Henares, Madrid , Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Royuela
mesh_terms: D000728:Androgens / Q000172:deficiency; D016923:Cell Death; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D016193:G1 Phase / Q000187:drug effects*; D006801:Humans; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D016196:S Phase / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000728:Androgens; D047428:Protein Kinase Inhibitors; D004815:Epidermal Growth Factor; D051550:I-kappa B Kinase; D048051:p38 Mitogen-Activated Protein Kinases
keywords: EGF; Prostate cancer; castration resistance; cell cycle; p38 MAPK; proliferation