title: ERK1/2 phosphorylation, induced by electromagnetic fields, diminishes during neoplastic transformation.
abstract: It has been suggested that electromagnetic (EM) fields can act as co-promoters during neoplastic transformation. To examine this possibility, we studied the effects of 0.8-, 8-, 80-, and 300-microT 60-Hz electromagnetic (EM) fields in INITC3H/10T1/2 mouse fibroblast cells. These cells are transformed carcinogenically by methylcholanthrene, but the neoplastic phenotype can be suppressed indefinitely by the presence of retinyl acetate (RAC) in the culture medium. The effects of EM field exposures were examined at three stages: (1) before initiation of transformation (i.e., RAC in the culture media); (2) early in the transformation process (4 days after withdrawal of RAC); and (3) at full of neoplastic transformation (10 days after withdrawal of RAC). EM field exposures induced significant increases in protein levels for hsp70 and c-Fos and in AP-1 binding activity. EM fields induced phosphorylation of MAPK/ERK1/2 before the onset of transformation, but these increases diminished during the transformation process. No phosphorylation in the other major extracellular stress pathway, SAPK/JNK, was detected in cells exposed to EM fields at any time before, during, or after neoplastic transformation. Human cells HL60, MCF7, and HTB124, exposed to EM fields, also showed MAPK/ERK1/2 phosphorylation. Cells treated with the phorbol ester, TPA, served as positive controls for AP-1 activation, c-Fos protein synthesis, and ERK1/2 phosphorylation. There was no indication that EM fields affected the rate of cell transformation or acted as a co-promoter, under the conditions of this study.
authors.affiliation: Department of Pathology, Columbia University, New York, NY 10032, USA.
authors.forename: M
authors.initials: M
authors.lastname: Jin
authors.forename: M
authors.initials: M
authors.lastname: Blank
authors.forename: R
authors.initials: R
authors.lastname: Goodman
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D002478:Cells, Cultured; D004247:DNA / Q000032:analysis; D004224:Diterpenes; D004574:Electromagnetic Fields; D004587:Electrophoresis, Agar Gel; D005347:Fibroblasts / Q000528:radiation effects; D050957:HSP110 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D000084562:Retinyl Esters; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D014801:Vitamin A / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D004224:Diterpenes; D050957:HSP110 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C121993:HSPA4 protein, human; D016760:Proto-Oncogene Proteins c-fos; D000084562:Retinyl Esters; D018808:Transcription Factor AP-1; D014801:Vitamin A; C009166:retinol acetate; D004247:DNA; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; D013755:Tetradecanoylphorbol Acetate