Abstract
Anticancer drugs stimulate apoptosis in the hair follicles (HF) and cause hair loss, the most common side effect of chemotherapy. In a mouse model for chemotherapy-induced hair loss, we demonstrate that p53 is essential for this process: in contrast to wild-type mice, p53-deficient mice show neither hair loss nor apoptosis in the HF keratinocytes that maintained active proliferation after cyclophosphamide treatment. HF in p53 mutants are characterized by down-regulation of Fas and insulin-like growth factor-binding protein 3 and by increased expression of Bcl-2. These observations indicate that local pharmacological inhibition of p53 may be useful to prevent chemotherapy-associated hair loss.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Alopecia / chemically induced*
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Alopecia / etiology
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Alopecia / metabolism
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Animals
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Antineoplastic Agents, Alkylating / toxicity*
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Apoptosis / drug effects
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Apoptosis / physiology
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Cyclophosphamide / toxicity*
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Down-Regulation / drug effects
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Female
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Hair Follicle / cytology
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Hair Follicle / drug effects
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Hair Follicle / metabolism
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Insulin-Like Growth Factor Binding Protein 3 / biosynthesis
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Insulin-Like Growth Factor Binding Protein 3 / genetics
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Proto-Oncogene Proteins c-bcl-2 / biosynthesis
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Tumor Suppressor Protein p53 / biosynthesis
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Tumor Suppressor Protein p53 / genetics
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Tumor Suppressor Protein p53 / physiology*
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Up-Regulation / drug effects
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fas Receptor / biosynthesis
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fas Receptor / genetics
Substances
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Antineoplastic Agents, Alkylating
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Insulin-Like Growth Factor Binding Protein 3
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Proto-Oncogene Proteins c-bcl-2
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Tumor Suppressor Protein p53
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fas Receptor
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Cyclophosphamide