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Malignancy without immortality? Cellular immortalization as a possible late event in melanoma progression

Soo, JK; Ross, ADM; Kallenberg, DM; Milagre, C; Chong, WH; Chow, J; Hill, L; Hoare, S; Collinson, RS; Hossain, M; et al. Soo, JK; Ross, ADM; Kallenberg, DM; Milagre, C; Chong, WH; Chow, J; Hill, L; Hoare, S; Collinson, RS; Hossain, M; Keith, WN; Marais, R; Bennett, DC (2011) Malignancy without immortality? Cellular immortalization as a possible late event in melanoma progression. PIGMENT CELL & MELANOMA RESEARCH, 24 (3). 490 - 503 (14). ISSN 1755-1471 https://doi.org/10.1111/j.1755-148X.2011.00850.x

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Abstract

P>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: beta-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.

Item Type: Article
Additional Information: PubMed ID: 21418545
Keywords: Anaphase, Aneuploidy, Cell Aging, Humans, Melanoma, Neoplasm Proteins, Nevus, Pigmented, Telomere, Tumor Cells, Cultured, Tumor Markers, Biological, Science & Technology, Life Sciences & Biomedicine, Oncology, Cell Biology, Dermatology, cell senescence, crisis, immortalization, primary melanoma, radial growth-phase, nevus, REPLICATIVE LIFE-SPAN, TELOMERASE ACTIVITY, TUMOR PROGRESSION, HUMAN-FIBROBLASTS, IN-VIVO, MELANOCYTIC LESIONS, GENE-EXPRESSION, ONCOGENIC RAS, HUMAN-CELLS, SENESCENCE, cell senescence, crisis, immortalization, primary melanoma, radial growth-phase, nevus
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Journal or Publication Title: PIGMENT CELL & MELANOMA RESEARCH
ISSN: 1755-1471
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DateEvent
1 June 2011Published
Web of Science ID: WOS:000290627800013
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URI: http://openaccess.sgul.ac.uk/id/eprint/1700
Publisher's version: https://doi.org/10.1111/j.1755-148X.2011.00850.x

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