Absence of distinguishing senescence traits in human melanocytic nevi

Sieu L. Tran, Sebastian Haferkamp, Lyndee L. Scurr, Kavitha Gowrishankar, Therese M. Becker, Chitra Desilva, John F. Thompson, Richard A. Scolyer, Richard F. Kefford, Helen Rizos*

*Corresponding author for this work

Research output: Contribution to journalArticle

32 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2226-2234
Number of pages9
JournalJournal of Investigative Dermatology
Volume132
Issue number9
DOIs
Publication statusPublished - Sep 2012
Externally publishedYes

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