title: Positivity of the proliferation marker Ki-67 in noncycling cells.
abstract: Ki-67 is a proliferation marker that is often used to estimate the growth fraction of tumors and other tissues. This antigen is expressed during all phases of the cell cycle but not in quiescent G0 cells. Many studies fail to indicate that the Ki-67 antigen can be expressed even when DNA synthesis is blocked. We studied the expression of the antigen Ki-67 in cycle-arrested osteosarcoma cells. We found that these cells are positive for Ki-67 even when they are arrested in G1/S or G2/M by using synchronizing inhibitors, by inducing p21(Waf1/Cip1) in a tetracycline-regulated expression system or by inducing wild type p53 and p21 after inflicting DNA damage. Our results show that not all cells containing the Ki-67 antigen are actively proliferating cells and we advise against the use of Ki-67 in studies on cells that overexpress p53 or p21.
authors.affiliation: Department of Haematology, Jordan Laboratory, University Hospital Utrecht, The Netherlands.
authors.forename: M G
authors.initials: MG
authors.lastname: van Oijen
authors.forename: R H
authors.initials: RH
authors.lastname: Medema
authors.forename: P J
authors.initials: PJ
authors.lastname: Slootweg
authors.forename: G
authors.initials: G
authors.lastname: Rijksen
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D015415:Biomarkers; D001859:Bone Neoplasms / Q000378:metabolism* / Q000473:pathology; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005434:Flow Cytometry; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism*; D009061:Mouth Mucosa / Q000378:metabolism / Q000473:pathology; D015739:Nocodazole / Q000494:pharmacology; D012516:Osteosarcoma / Q000378:metabolism* / Q000473:pathology; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53; D015739:Nocodazole; D006918:Hydroxyurea