title: Expression and activation of P38 MAP kinase in invasive ductal breast cancers: correlation with expression of the estrogen receptor, HER2 and downstream signaling phosphorylated proteins.
abstract: MAP kinase signaling proteins have major implications in the molecular oncogenesis of breast cancers and have been extensively investigated as putative targets for therapy. This study reports the investigation of the expression of P38 MAPK and its phosphorylated form (p-P38 MAPK) in clinical specimens of invasive breast carcinomas and their correlation with estrogen receptor (ER) and HER2 expression, as well as MAPK and PI3 kinase-AKT pathway signaling phosphorylated proteins. Expression levels of P38 MAPK and p-P38 MAPK as well as p-AKT, p-GSK3β, p-S6 kinase, p-MEK1 and p-ERK1/2 were quantitatively assessed using multiplex bead immunoassay in frozen specimens from 45 invasive ductal breast cancers. Twenty-nine specimens were ER+, 15 were HER2+ and 10 were triple‑negative breast cancers (TNBCs). P38 MAPK was found to be expressed in all tumor specimens and was significantly (P=0.002) overexpressed in ER+ tumors. P38 MAPK expression was lower in TNBCs than in all of the other tumors. The median expression of p-P38 MAPK was also higher in ER+ tumors while lower in the TNBCs. HER2 status had no effect on P38 MAPK and p-P38 MAPK expression. No variation in the phosphorylation rate of P38 MAPK was observed in relation with ER, HER2 or TNBC status. Significantly higher (P=0.0048) expression of p-AKT was observed in HER2+ tumors. No significant difference in p-MEK1, p-GSK3β and p-S6K expression was found in any other comparisons based on ER and HER2 expression subtypes. Investigation of the expression of multiple phosphorylated signaling proteins can be used for personalized targeted therapy. In invasive breast cancer, the overexpression of P38 MAPK may serve as a biomarker for the evaluation of P38 MAPK inhibitors.
authors.affiliation: Department of Biopathology, Institut de Cancérologie de Lorraine, 54519 Vandoeuvre les Nancy, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Merlin
authors.forename: Alexandre
authors.initials: A
authors.lastname: Harlé
authors.forename: Maëva
authors.initials: M
authors.lastname: Lion
authors.forename: Carole
authors.initials: C
authors.lastname: Ramacci
authors.forename: Agnès
authors.initials: A
authors.lastname: Leroux
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000378:metabolism; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000096:biosynthesis / Q000378:metabolism; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000096:biosynthesis / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D048369:MAP Kinase Kinase 1 / Q000096:biosynthesis / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000235:genetics; D008875:Middle Aged; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000096:biosynthesis / Q000378:metabolism*; D019893:Ribosomal Protein S6 Kinases / Q000096:biosynthesis / Q000378:metabolism; D064726:Triple Negative Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D048049:Extracellular Signal-Regulated MAP Kinases; D038362:Glycogen Synthase Kinase 3; D000071679:Glycogen Synthase Kinase 3 beta; D048369:MAP Kinase Kinase 1; D051057:Proto-Oncogene Proteins c-akt; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D019893:Ribosomal Protein S6 Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C508053:ERBB2 protein, human; C000605506:GSK3B protein, human; C482125:MAP2K1 protein, human