p53 is essential for chemotherapy-induced hair loss.
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.
Botchkarev
V A
VA
Department of Dermatology, Boston University School of Medicine, Massachusetts 02118, USA. vladbotc@bu.edu
Komarova
E A
EA
Siebenhaar
F
F
Botchkareva
N V
NV
Komarov
P G
PG
Maurer
M
M
Gilchrest
B A
BA
Gudkov
A V
AV
D000505:Alopecia / Q000139:chemically induced* / Q000209:etiology / Q000378:metabolism; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D003520:Cyclophosphamide / Q000633:toxicity*; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D018859:Hair Follicle / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015854:Up-Regulation / Q000187:drug effects; D019014:fas Receptor / Q000096:biosynthesis / Q000235:genetics
D018906:Antineoplastic Agents, Alkylating; D018972:Insulin-Like Growth Factor Binding Protein 3; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D019014:fas Receptor; D003520:Cyclophosphamide