Universität zu Köln

Friedrichs, Jacqueline, Fink, Dennis, Mauch, Cornelia, Kindler, Dagmar, Hartmann, Wolfgang ORCID: 0000-0002-7609-5021, Schuele, Roland, Buettner, Reinhard and Friedrichs, Nicolaus (2015). TGF-beta 1-dependent induction and nuclear translocation of FHL2 promotes keratin expression in pilomatricoma. Virchows Arch., 466 (2). S. 199 - 209. NEW YORK: SPRINGER. ISSN 1432-2307

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Abstract

Pilomatricoma is a tumour derived from hair matrix cells, which shows progressive keratin expression. Tumorigenesis is frequently associated with activating mutations in beta-catenin gene inducing nuclear expression of beta-catenin protein. The present study analysed the role of transforming growth factor-beta 1 (TGF-beta 1) 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-beta 1 and nuclear FHL2 expression in the outer root sheath layer separated from nuclear beta-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-beta 1 and nuclear FHL2 in tumour cells, which mostly lacked nuclear beta-catenin expression. Tumoural proliferation (ki67) was associated with nuclear beta-catenin staining but not with expression of nuclear FHL2. In early pilomatricomas, TGF-beta 1 expression was observed in few peripheral tumour cells showing absent or faint nuclear FHL2 co-staining. TGF-beta 1 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-beta 1 expression; in case of enhanced TGF-beta 1 expression associated with keratin 10 staining. TGF-beta 1-treatment of cultured human keratinocytes induced nuclear and cytoplasmatic FHL2 staining as well as keratin 14 staining. Accordingly, siRNA-mediated FHL2 knockdown of TGF-beta 1-stimulated keratinocytes reduced keratin 14 staining. In conclusion, tumoural TGF-beta 1 secretion seems to induce nuclear translocation of co-factor FHL2 mediating progressive keratin expression in pilomatricoma.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Friedrichs, Jacqueline UNSPECIFIED UNSPECIFIED UNSPECIFIED Fink, Dennis UNSPECIFIED UNSPECIFIED UNSPECIFIED Mauch, Cornelia UNSPECIFIED UNSPECIFIED UNSPECIFIED Kindler, Dagmar UNSPECIFIED UNSPECIFIED UNSPECIFIED Hartmann, Wolfgang UNSPECIFIED orcid.org/0000-0002-7609-5021 UNSPECIFIED Schuele, Roland UNSPECIFIED UNSPECIFIED UNSPECIFIED Buettner, Reinhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Friedrichs, Nicolaus UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-413545
DOI:	10.1007/s00428-014-1692-5
Journal or Publication Title:	Virchows Arch.
Volume:	466
Number:	2
Page Range:	S. 199 - 209
Date:	2015
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1432-2307
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language BETA-CATENIN; RECEPTOR; SKIN; DIFFERENTIATION; PROTEIN; MUTATIONS; LESSONS; CANCER; TUMORS Multiple languages Pathology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/41354