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Malignancy without immortality? Cellular immortalization as a possible late event in melanoma progression
Author(s) -
Soo Julia K.,
MacKenzie Ross Alastair D.,
Kallenberg David M.,
Milagre Carla,
Heung Chong W.,
Chow Jade,
Hill Lucy,
Hoare Stacey,
Collinson Rebecca S.,
Hossain Mehnaz,
Keith W. Nicol,
Marais Richard,
Bennett Dorothy C.
Publication year - 2011
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/j.1755-148x.2011.00850.x
Subject(s) - telomerase , telomere , melanoma , biology , senescence , cancer research , cell culture , telomerase reverse transcriptase , pathology , microbiology and biotechnology , medicine , genetics , dna , gene
Summary Cell senescence is a permanent growth arrest following extended proliferation. Cultured cancer cells including metastatic melanoma cells often appear immortal (proliferate indefinitely), while uncultured benign nevi (moles) show senescence markers. Here, with new explantation methods, we investigated which classes of primary pigmented lesions are typically immortal. Nevi yielded a few proliferating cells, consistent with most nevus cells being senescent. No nevus culture (0/28) appeared immortal. Some thin and thick melanoma cultures proved immortal under these conditions, but surprisingly few (4/37). All arrested cultures displayed three senescence markers in some cells: β‐galactosidase, nuclear p16, and heterochromatic foci/aggregates. However, melanoma cultures also showed features of telomeric crisis (arrest because of ultrashort telomeres). Moreover, crisis markers including anaphase bridges were frequent in uncultured vertical growth‐phase (VGP) melanomas. Conversely, all immortal melanoma cultures expressed telomerase reverse transcriptase and telomerase, showing aneuploidy. The findings suggest that primary melanomas are typically precrisis, with immortalization/telomere maintenance as a late event.