Abstract
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 p16 INK4A may 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.
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Acknowledgments
N.F.B. was funded by NIH/NCI 5R01CA74592, NIH/NCI 1R01CA190533, NIH/NIAMS 1R03AR066880, and NIH/NCATS UL1 RR025780. T.T. was funded by NIH/NIAMS 1K01AR063203-01, NIH/NC 1R03CA191937, CCTSI Research grant from NIH/NCATS UL1 RR025780, ACS IRG 57-001-53 from the American Cancer Society and a Dermatology Foundation research grant.
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Joselow, A., Lynn, D., Terzian, T., Box, N.F. (2017). Senescence-Like Phenotypes in Human Nevi. In: Nikiforov, M. (eds) Oncogene-Induced Senescence. Methods in Molecular Biology, vol 1534. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6670-7_17
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DOI: https://doi.org/10.1007/978-1-4939-6670-7_17
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