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Human cutaneous int...
Human cutaneous interfollicular melanocytes differentiate temporarily under genotoxic stress
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- Fessé, Per (author)
- Uppsala universitet,Centrum för klinisk forskning, Gävleborg,Institutionen för immunologi, genetik och patologi
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- Nyman, Jan, 1956 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för onkologi,Institute of Clinical Sciences, Department of Oncology,Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Onco, Gothenburg, Sweden.
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- Hermansson, I. (author)
- Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Onco, Gothenburg, Sweden.
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- Book, Majlis (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
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- Ahlgren, J. (author)
- Örebro Univ, Fac Med & Hlth, Dept Oncol, Örebro, Sweden.
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- Turesson, Ingela (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
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(creator_code:org_t)
- Elsevier BV, 2022
- 2022
- English.
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In: Iscience. - : Elsevier BV. - 2589-0042. ; 25:10
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Abstract
Subject headings
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- DNA-damage response of cutaneous interfollicular melanocytes to fractionated radiotherapy was investigated by immunostaining of tissue sections from punch biopsies collected before, during, and after the treatment of patients for breast cancer. Our clinical assay with sterilized hair follicles, excluded the migration of immature melanocytes from the bulge, and highlighted interfollicular melanocytes as an autonomous self-renewing population. About thirty percent are immature. Surrounding keratinocytes induced and maintained melanocyte differentiation as long as treatment was ongoing. Concomitant with differentiation, melanocytes were protected from apoptosis by transient upregulation of Bcl-2 and CXCR2. CXCR2 upregulation also indicated the instigation of premature senescence, preventing proliferation. The stem cell factor BMI1 was constitutively expressed exclusively in interfollicular melanocytes and further upregulated upon irradiation. BMI1 prevents apoptosis, terminal differentiation, and premature senescence, allowing dedifferentiation post-treatment, by suppressing the p53/p21-and p16-mediated response and upregulating CXCR2 to genotoxic damage. The pre-treatment immature subset of interfollicular melanocytes was restored after the exposure ended.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Radiologi och bildbehandling (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Radiology, Nuclear Medicine and Medical Imaging (hsv//eng)
Keyword
- self-renewal
- uv-radiation
- DNA-damage
- human skin
- cell-proliferation
- tumor suppression
- wnt/beta-catenin
- expression
- melanoma
- protein
- Science & Technology - Other Topics
- Cancer
Publication and Content Type
- ref (subject category)
- art (subject category)
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