title: Hair follicle apoptosis and Bcl-2.
abstract: Hair follicle (HF) morphogenesis and cycling are characterized by a tightly controlled balance of proliferation, differentiation and apoptosis. The members of the bcl-2 family of proto-oncogenes are important key players in the apoptosis control machinery of most cell types. Bcl-2, an apoptosis inhibitor, and Bax, an apoptosis promoter, show tightly regulated, hair cycle-dependent expression patterns: during catagen, the distal ORS of the HF remains strongly positive for Bcl-2 and Bax; in contrast, the proximal epithelial part of the HF loses most Bcl-2 expression while it remains strongly positive for Bax. In Bcl-2 null mice, skin becomes markedly hypopigmented during the first postnatal anagen probably due to increased melanocyte apoptosis. Reportedly, these mice also show a retardation of the first anagen development after birth. Transgenic mice overexpressing Bcl-2 under the control of the keratin-1 promoter display multifocal epidermal hyperplasia and aberrant expression of keratin-6, while alterations of HF cycling have not been investigated. Surprisingly, Bcl-2 overexpression under the control of the keratin-14 promoter leads to accelerated catagen progression and increased chemotherapy-induced apoptosis, HF dystrophy and alopecia. Transgenic mice overexpressing Bcl-X(L), another anti-apoptotic bcl-2 family member, under the control of the K14 promoter, reportedly also display accelerated catagen development. These and other Bcl-2 transgenic and null mice are now available to further dissect the as yet unclear, and likely complex, role of Bcl-2 in HF growth and pigmentation.
authors.affiliation: Centre for Cutaneous Research, Queen Mary and Westfield College, London, UK. mueller-rover@gmx.net
authors.forename: S
authors.initials: S
authors.lastname: Müller-Röver
authors.forename: H
authors.initials: H
authors.lastname: Rossiter
authors.forename: G
authors.initials: G
authors.lastname: Lindner
authors.forename: E M
authors.initials: EM
authors.lastname: Peters
authors.forename: T S
authors.initials: TS
authors.lastname: Kupper
authors.forename: R
authors.initials: R
authors.lastname: Paus
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D005786:Gene Expression Regulation; D019254:Genes, bcl-2; D018859:Hair Follicle / Q000473:pathology* / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2