title: Abrogation of the p38 MAPK α signaling pathway does not promote radioresistance but its activity is required for 5-Fluorouracil-associated radiosensitivity.
abstract: The p38 Mitogen Activated Protein Kinase (MAPK) signaling pathway has become a major player in the response to DNA-damage. A growing body of evidences has been relating this signaling pathway to the cellular response to ionizing radiation (IR), suggesting a role in radioresistance. Here, we study the implication of this signaling pathway in the response to IR in terms of radioresistance. To this end we used 10 different cell lines derived from several types of tumors (colorectal, non-small cell lung cancer -NSCLC-, renal and glioblastoma). Although p38 MAPK is transiently activated by IR, our data, obtained by genetic and chemical approaches, showed that this signaling pathway is not implicated in cellular viability after IR exposure. Indeed, down-modulation of this signaling pathway promotes a mild radiosensitivity depending on the cell line. However, it is remarkable that lack of p38 MAPK α abrogates the radiosensitizing effect of 5-Fluorouracil (5-FU) in HCT116 cell line, supporting the role of this MAPK in the radiosensitizing action of 5-FU.
authors: Laboratorio de Oncología Molecular, Centro Regional de Investigaciones Biomédicas (CRIB), UCLM, 02006 Albacete, Spain.
authors: Miguel A
authors: MA
authors: de la Cruz-Morcillo
authors: Jesús
authors: J
authors: García-Cano
authors: Laura
authors: L
authors: Arias-González
authors: Elena
authors: E
authors: García-Gil
authors: Francisco
authors: F
authors: Artacho-Cordón
authors: Sandra
authors: S
authors: Ríos-Arrabal
authors: María L
authors: ML
authors: Valero
authors: Francisco J
authors: FJ
authors: Cimas
authors: Leticia
authors: L
authors: Serrano-Oviedo
authors: María V
authors: MV
authors: Villas
authors: Jesús
authors: J
authors: Romero-Fernández
authors: María I
authors: MI
authors: Núñez
authors: Ricardo
authors: R
authors: Sánchez-Prieto
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D005472:Fluorouracil / Q000494:pharmacology*; D015870:Gene Expression; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D020935:MAP Kinase Signaling System; D048308:Mitogen-Activated Protein Kinase 14 / Q000235:genetics / Q000378:metabolism*; D011836:Radiation Tolerance / Q000187:drug effects*
chemical_list: D000964:Antimetabolites, Antineoplastic; D048308:Mitogen-Activated Protein Kinase 14; D005472:Fluorouracil