TGF-β1-dependent induction and nuclear translocation of FHL2 promotes keratin expression in pilomatricoma.

Abstract

Pilomatricoma is a tumour derived from hair matrix cells, which shows progressive keratin expression. Tumorigenesis is frequently associated with activating mutations in β-catenin gene inducing nuclear expression of β-catenin protein. The present study analysed the role of transforming growth factor-β1 (TGF-β1) and four-and-a-half LIM domain protein 2 (FHL2) in pilomatricoma in synopsis with their expression patterns in human anagen hair. Human anagen hair showed TGF-β1 and nuclear FHL2 expression in the outer root sheath layer separated from nuclear β-catenin staining, which was observed in cells of matrix and inner root sheath layers. Correspondingly, 41 out of 50 pilomatricomas showed co-labelling of TGF-β1 and nuclear FHL2 in tumour cells, which mostly lacked nuclear β-catenin expression. Tumoural proliferation (ki67) was associated with nuclear β-catenin staining but not with expression of nuclear FHL2. In early pilomatricomas, TGF-β1 expression was observed in few peripheral tumour cells showing absent or faint nuclear FHL2 co-staining. TGF-β1 expression extended in growing tumours going along with strong nuclear FHL2 co-labelling as well as progressive keratin 14 and keratin 1 expression. In vitro, cultured human keratinocytes showed weak to marked autocrine TGF-β1 expression; in case of enhanced TGF-β1 expression associated with keratin 10 staining. TGF-β1-treatment of cultured human keratinocytes induced nuclear and cytoplasmatic FHL2 staining as well as keratin 14 staining. Accordingly, siRNA-mediated FHL2 knockdown of TGF-β1-stimulated keratinocytes reduced keratin 14 staining. In conclusion, tumoural TGF-β1 secretion seems to induce nuclear translocation of co-factor FHL2 mediating progressive keratin expression in pilomatricoma.

• Authors: Jacqueline Friedrichs, Dennis Fink, Cornelia Mauch, Dagmar Kindler, Wolfgang Hartmann, Roland Schüle, Reinhard Buettner, Nicolaus Friedrichs
• Journal: Virchows Archiv : an international journal of pathology (Virchows Arch) Vol. 466 Issue 2 Pg. 199-208 (Feb 2015) ISSN: 1432-2307 [Electronic] Germany
• PMID: 25477051 (Publication Type: Journal Article)

Chemical References

• FHL2 protein, human
• LIM-Homeodomain Proteins
• Muscle Proteins
• Transcription Factors
• Transforming Growth Factor beta1
• Keratins

Topics

• Active Transport, Cell Nucleus (physiology)
• Adolescent
• Adult
• Aged
• Child
• Child, Preschool
• Female
• Hair Diseases (metabolism, pathology)
• Humans
• Immunohistochemistry
• Infant
• Infant, Newborn
• Keratins (biosynthesis)
• LIM-Homeodomain Proteins (metabolism)
• Male
• Middle Aged
• Muscle Proteins (metabolism)
• Pilomatrixoma (metabolism, pathology)
• Skin Neoplasms (metabolism, pathology)
• Transcription Factors (metabolism)
• Transforming Growth Factor beta1 (metabolism)
• Young Adult