Senescence-Like Phenotypes in Human Nevi.
Cellular senescence is an irreversible arrest of cell proliferation at the G1 stage of the cell cycle in which cells become refractory to growth stimuli. Senescence is a critical and potent defense mechanism that mammalian cells use to suppress tumors. While there are many ways to induce a senescence response, oncogene-induced senescence (OIS) remains the key to inhibiting progression of cells that have acquired oncogenic mutations. In primary cells in culture, OIS induces a set of measurable phenotypic and behavioral changes, in addition to cell cycle exit. Senescence-associated β-Galactosidase (SA-β-Gal) activity is a main hallmark of senescent cells, along with morphological changes that may depend on the oncogene that is activated, or on the primary cell type. Characteristic cellular changes of senescence include increased size, flattening, multinucleation, and extensive vacuolation. At the molecular level, tumor suppressor genes such as p53 and p16INK4Amay play a role in initiation or maintenance of OIS. Activation of a DNA damage response and a senescence-associated secretory phenotype could delineate the onset of senescence. Despite advances in our understanding of how OIS suppresses some tumor types, the in vivo role of OIS in melanocytic nevi and melanoma remains poorly understood and not validated. In an effort to stimulate research in this field, we review in this chapter the known markers of senescence and provide experimental protocols for their identification by immunofluorescent staining in melanocytic nevi and malignant melanoma.
Charles C. Gates Center for Regenerative Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.|Department of Dermatology, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.|School of Medicine, Tulane University, New Orleans, LA, USA.
Andrew
A
Joselow
Charles C. Gates Center for Regenerative Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.|Department of Dermatology, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.
Darren
D
Lynn
Charles C. Gates Center for Regenerative Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.|Department of Dermatology, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.
Tamara
T
Terzian
Department of Dermatology, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA. neil.box@ucdenver.edu.|Charles C. Gates Center for Regenerative Medicine, University of Colorado, Anschutz Medical Campus, RC1-North, P18-8132, Aurora, CO, 80045, USA. neil.box@ucdenver.edu.
Neil F
NF
Box
D015415:Biomarkers; D002460:Cell Line; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D009506:Nevus / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics / Q000378:metabolism; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D001616:beta-Galactosidase / Q000378:metabolism
D015415:Biomarkers; D019941:Cyclin-Dependent Kinase Inhibitor p16; D016159:Tumor Suppressor Protein p53; D048493:Proto-Oncogene Proteins B-raf; D001616:beta-Galactosidase
BRAF; Cancer; DNA damage; Galactosidase; Immunofluorescence; Melanoma; Nevus; Oncogene; Protocol; Senescence; p16INK4A; p53