دورية أكاديمية
أعرض في EDS

Cellular senescence in naevi and immortalisation in melanoma: a role for p16?

التفاصيل البيبلوغرافية
العنوان: Cellular senescence in naevi and immortalisation in melanoma: a role for p16?
المؤلفون: Gray-Schopfer VC; Division of Basic Medical Sciences, St George's, University of London, Cranmer Terrace, London SW17 0RE, UK., Cheong SC, Chong H, Chow J, Moss T, Abdel-Malek ZA, Marais R, Wynford-Thomas D, Bennett DC
المصدر: British journal of cancer [Br J Cancer] 2006 Aug 21; Vol. 95 (4), pp. 496-505. Date of Electronic Publication: 2006 Aug 01.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group on behalf of Cancer Research UK Country of Publication: England NLM ID: 0370635 Publication Model: Print-Electronic Cited Medium: Print ISSN: 0007-0920 (Print) Linking ISSN: 00070920 NLM ISO Abbreviation: Br J Cancer Subsets: MEDLINE
أسماء مطبوعة: Publication: 2002- : London : Nature Publishing Group on behalf of Cancer Research UK
Original Publication: London, Lewis.
مواضيع طبية MeSH: Cellular Senescence*, Cyclin-Dependent Kinase Inhibitor p16/*physiology , Melanoma/*pathology , Nevus/*pathology , Skin Neoplasms/*pathology, Cell Survival ; Cells, Cultured ; Cyclin-Dependent Kinase Inhibitor p21/metabolism ; Disease Progression ; Humans ; Melanocytes/metabolism ; Proto-Oncogene Proteins B-raf/pharmacology ; Tumor Suppressor Protein p53/metabolism
مستخلص: Cellular senescence, the irreversible proliferative arrest seen in somatic cells after a limited number of divisions, is considered a crucial barrier to cancer, but direct evidence for this in vivo was lacking until recently. The best-known form of human cell senescence is attributed to telomere shortening and a DNA-damage response through p53 and p21. There is also a more rapid form of senescence, dependent on the p16-retinoblastoma pathway. p16 (CDKN2A) is a known melanoma susceptibility gene. Here, we use retrovirally mediated gene transfer to confirm that the normal form of senescence in cultured human melanocytes involves p16, since disruption of the p16/retinoblastoma pathway is required as well as telomerase activation for immortalisation. Expression (immunostaining) patterns of senescence mediators and markers in melanocytic lesions provide strong evidence that cell senescence occurs in benign melanocytic naevi (moles) in vivo and does not involve p53 or p21 upregulation, although p16 is widely expressed. In comparison, dysplastic naevi and early (radial growth-phase, RGP) melanomas show less p16 and some p53 and p21 immunostaining. All RGP melanomas expressed p21, suggesting areas of p53-mediated senescence, while most areas of advanced (vertical growth-phase) melanomas lacked both p16 and p21, implying escape from both forms of senescence (immortalisation). Moreover, nuclear p16 but not p21 expression can be induced in human melanocytes by oncogenic BRAF, as found in around 80% of naevi. We conclude that cell senescence can form a barrier to melanoma development. This also provides a potential explanation of why p16 is a melanoma suppressor gene.
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معلومات مُعتمدة: 06-0062 United Kingdom AICR_ Worldwide Cancer Research
المشرفين على المادة: 0 (Cyclin-Dependent Kinase Inhibitor p16)
0 (Cyclin-Dependent Kinase Inhibitor p21)
0 (Tumor Suppressor Protein p53)
EC 2.7.11.1 (BRAF protein, human)
EC 2.7.11.1 (Proto-Oncogene Proteins B-raf)
تواريخ الأحداث: Date Created: 20060802 Date Completed: 20060915 Latest Revision: 20220227
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC2360676
DOI: 10.1038/sj.bjc.6603283
PMID: 16880792
قاعدة البيانات: MEDLINE
الوصف
تدمد:0007-0920
DOI:10.1038/sj.bjc.6603283