title: AP-1 and heat shock protein 27 expression in human astrocytomas.
abstract: OBJECTIVE
  In previous work we have shown that the expression of heat shock protein 27 (Hsp27) is associated with anaplastic potential of astrocytomas (Anticancer Res 1997, 17:2677-2682). Heat shock protein-coding genes have been found to have a putative AP-1 (activator protein-1)-binding site in their promoter region and the synthesis of these proteins is induced by the same extracellular stimuli that also activate AP-1 (a homo/heterodimer of members of the Jun and Fos families). In order to detect the putative relation of Hsp27 with AP-1 activation in human astrocytomas we examined eighty astrocytic tumors with different grades of malignancy for c-Jun, c-Fos, and Hsp27 expression.
  
  
  METHODS
  Six pilocytic astrocytomas (WHO grade I), 15 diffuse fibrillary astrocytomas (WHO grade II), 19 anaplastic astrocytomas (WHO grade III), and 40 glioblastomas multiforme (WHO grade IV), were studied by immunohistochemistry using monoclonal and polyclonal antibodies directed against human Hsp27, c-Fos, and active (phosphorylated) forms of c-Jun (p-c-Jun). Monoclonal antibodies against the phosphorylated forms of the over-expressed MAP kinases JNK (c-Jun N-terminal kinase) (p-JNK) and p38 (p-p38) were also used.
  
  
  RESULTS
  Overexpression of p-c-Jun, c-Fos and p-JNK was observed in the majority of glioblastomas (grade IV) whereas only minimal expression was noted in diffuse fibrillary astrocytomas (grade II). Hsp27 expression was observed only in the tumor specimens where c-Jun and c-Fos were co-expressed. AP-1/Hsp27 co-expression was associated with ascending grading of malignancy and it was independent of the proliferation index of the tumors.
  
  
  CONCLUSIONS
  Our findings suggest that during malignant progression of astrocytomas there is activation of signal transduction cascade(s) culminating in AP-1 induction.
authors.affiliation: Department of Anatomy, School of Medicine, University of Patras, Greece. massim@med.upatras.gr
authors.forename: M
authors.initials: M
authors.lastname: Assimakopoulou
authors.forename: J
authors.initials: J
authors.lastname: Varakis
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001254:Astrocytoma / Q000737:chemistry* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006360:Heat-Shock Proteins / Q000032:analysis*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000032:analysis; D018808:Transcription Factor AP-1 / Q000032:analysis*
chemical_list: D006360:Heat-Shock Proteins; D019394:Ki-67 Antigen; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases