On the Regulation of Hair Keratin Expression: Lessons from Studies in Pilomatricomas

• Published in: Journal of investigative dermatology Vol. 122; no. 5; pp. 1078 - 1083
• Main Authors: Cribier, Bernard, Peltre, Bernard, Grosshans, Edouard, Langbein, Lutz, Schweizer, Jürgen
• Format: Journal Article
• Language: English
• Published: Danvers, MA Elsevier Inc 01.05.2004; Nature Publishing; Elsevier Limited
• Subjects: beta Catenin; Biological and medical sciences; Cytoskeletal Proteins - metabolism; Dermatology; DNA-Binding Proteins - metabolism; Hair Diseases - metabolism; Hair Diseases - pathology; Hair Follicle - metabolism; Hair Follicle - pathology; hair follicles; Homeodomain Proteins - metabolism; human; Humans; Immunohistochemistry; Keratin-5; Keratins - metabolism; Lymphoid Enhancer-Binding Factor 1; Medical sciences; Pilomatrixoma - metabolism; Pilomatrixoma - pathology; Signal Transduction - physiology; Skin Neoplasms - metabolism; Skin Neoplasms - pathology; Trans-Activators - metabolism; transcription factors; Transcription Factors - metabolism; tumors; Tumors of the skin and soft tissue. Premalignant lesions; hair follicles; tumors; transcription factors; human; Human; Hair; Keratin; Skin disease; Regulation(control); Dermatology; hair follicles/human/transcription factors/tumors; Benign calcifying epithelioma of Malherbe; Benign neoplasm
• ISSN: 0022-202X; 1523-1747
• DOI: 10.1111/j.0022-202X.2004.22513.x

Human hair follicles exhibit a complex pattern of sequential hair keratin expression in the hair matrix, cuticle, and cortex. In pilomatricomas, that is, benign skin tumors thought to arise from germinative matrix cells of the hair follicle and retaining morphological signs of cortical differentiation, this differential hair keratin pattern has been shown to be faithfully preserved in the lower and upper transitional cell compartments of the tumors. Here we show that also the co-expression of hair keratin hHa5 with its regulatory nuclear homeoprotein HOXC13 in matrix cells of the hair follicle is maintained in lower transitional cells of pilomatricomas. In contrast, the nuclear co-expression of LEF1 and β-catenin, which in the hair follicle has been postulated to initiate cortex cell differentiation through the induction of hair keratin hHa1 expression (Merill et al, Genes Dev 15:1688–1705, 2001), is not preserved in upper transitional cells of pilomatricomas. Although these cells correctly express hHa1, they are completely devoid of LEF1 and nuclear LEF1/β-catenin co-expression is shifted to a subpopulation of hair keratin-free basaloid cells of the tumors. These data imply that unlike the normal hair follicle, cortical differentiation in pilomatricomas is not under the control of the canonical Wnt signaling pathway.