title: Absence of distinguishing senescence traits in human melanocytic nevi.
abstract: Cellular senescence permanently restricts the replicative capacity of cells in response to various stress signals, including aberrant activation of oncogenes. The presence of predictive senescence markers in human premalignant lesions suggests that senescence may function as a genuine tumor suppressor. These markers are not exclusive to the senescence program, however, and it is possible that their expression in vivo does not discriminate irreversible from reversible forms of proliferative arrest. In this study, we aimed to clarify whether human nevus cells can be distinguished from primary and transformed melanocytes by examining the expression of eight senescence markers, including those previously purported to define nevi as senescent tumors. Specifically, we analyzed effectors of senescence, including p16(INK4a), p53, and DNA damage (γ-H2AX), as well as predictive markers of senescence including Ki67, PML, senescence-associated β-galactosidase, heterochromatic foci (H3K9Me, 4'-6-diamidino-2-phenylindole), and nuclear size. We found that these commonly accepted senescence markers do not in fact distinguish nevi from precursor/normal and transformed/malignant melanocytes. We conclude that on the basis of current evidence it cannot be reasonably inferred that nevi are permanently growth arrested via senescence.
authors.affiliation: Westmead Institute for Cancer Research, University of Sydney at Westmead Millennium Institute, Westmead Hospital, Westmead, New South Wales, Australia.
authors.forename: Sieu L
authors.initials: SL
authors.lastname: Tran
authors.forename: Sebastian
authors.initials: S
authors.lastname: Haferkamp
authors.forename: Lyndee L
authors.initials: LL
authors.lastname: Scurr
authors.forename: Kavitha
authors.initials: K
authors.lastname: Gowrishankar
authors.forename: Therese M
authors.initials: TM
authors.lastname: Becker
authors.forename: Chitra
authors.initials: C
authors.lastname: Desilva
authors.forename: John F
authors.initials: JF
authors.lastname: Thompson
authors.forename: Richard A
authors.initials: RA
authors.lastname: Scolyer
authors.forename: Richard F
authors.initials: RF
authors.lastname: Kefford
authors.forename: Helen
authors.initials: H
authors.lastname: Rizos
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry; D016922:Cellular Senescence; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis / Q000378:metabolism; D004249:DNA Damage; D006657:Histones / Q000032:analysis / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000032:analysis / Q000378:metabolism; D019394:Ki-67 Antigen / Q000032:analysis / Q000378:metabolism; D009508:Nevus, Pigmented / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000032:analysis / Q000378:metabolism; D000071156:Promyelocytic Leukemia Protein; D012878:Skin Neoplasms / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D014157:Transcription Factors / Q000032:analysis / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000378:metabolism; D001616:beta-Galactosidase / Q000032:analysis / Q000378:metabolism
chemical_list: D015415:Biomarkers; D019941:Cyclin-Dependent Kinase Inhibitor p16; C468783:H2AX protein, human; D006657:Histones; D007211:Indoles; D019394:Ki-67 Antigen; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; C495901:TP53 protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C070576:PML protein, human; C007293:DAPI; D001616:beta-Galactosidase