title: Concerted overexpression of the genes encoding p21 and cyclin D1 is associated with growth inhibition and differentiation in various carcinomas.
abstract: OBJECTIVE
  To investigate the expression of the genes encoding cyclin D1 and p21 in proliferative and non-proliferative cells, as demonstrated by the Ki67 antibody, and to correlate these findings with differentiation.
  
  
  METHODS
  Immunohistochemistry and immunofluorescence double staining were performed on three breast cancers, two squamous cell cancers of the head and neck, and one ovarium cystadenocarcinoma. In addition, the in vitro effect of cyclin D1 on p21 gene expression in MCF7 breast cancer cells was evaluated.
  
  
  RESULTS
  Immunofluorescence double staining showed a differentiation related gradient in the detection of the Ki67 antigen, cyclin D1, and p21 in squamous cell cancers of the head and neck: Ki67 was detected in the basal layers of the tumour and the cyclin D1 and p21 genes were coexpressed in the higher, more differentiated layers of the tumour. The breast and ovarian cancers often had cells that coexpressed the p21 and cyclin D1 genes, whereas coexpression of cyclin D1 and Ki67 did not occur. Western blot analysis of the MCF7 breast cancer cells showed an upregulation of p21 production when cyclin D1 gene expression was induced.
  
  
  CONCLUSIONS
  Overexpression of the cyclin D1 gene seems to lead to growth arrest in a variety of human cancers, possibly through the induction of p21 by cyclin D1. In squamous cell cancer, concerted overexpression of the genes encoding cyclin D1 and p21 might also induce differentiation.
authors.affiliation: Department of Pathology, Academic Hospital Vrije Universiteit, Amsterdam, The Netherlands.
authors.forename: J S
authors.initials: JS
authors.lastname: de Jong
authors.forename: P J
authors.initials: PJ
authors.lastname: van Diest
authors.forename: R J
authors.initials: RJ
authors.lastname: Michalides
authors.forename: J P
authors.initials: JP
authors.lastname: Baak
mesh_terms: D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007124:Immunoenzyme Techniques; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D009363:Neoplasm Proteins; D019938:Cyclin D1