Title: Anchorage-dependent expression of the vitamin D receptor in normal human keratinocytes
Authors: Segaert, Siegfried ×
Garmyn, Maria
Degreef, Hugo
Bouillon, Roger #
Issue Date: Oct-1998
Publisher: Elsevier Science Pub. Co.
Series Title: Journal of Investigative Dermatology vol:111 issue:4 pages:551-8
Abstract: Although the nuclear vitamin D receptor (VDR) is involved in the control of keratinocyte proliferation and differentiation by its ligand 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], its role in epidermal physiology remains poorly understood. Because VDR abundance reflects cellular responsiveness to 1,25(OH)2D3, we investigated VDR expression in cultured human keratinocytes and identified cell anchorage and cytoskeletal integrity as essential requirements for the maintenance of VDR levels. Suspension culture rapidly suppressed VDR expression and 1,25(OH)2D3 responsiveness (as estimated by induction of 24-hydroxylase mRNA), due to decreased transcription of the VDR gene. Concomitantly, overt growth arrest with p21WAF1 induction and cyclin D1 and c-myc suppression occurred, together with induction of differentiation markers and retinoid X receptor alpha, the heterodimeric partner for VDR. Reattachment of suspended keratinocytes to fibronectin led to a rapid restoration of VDR expression, which could be blocked by RGD peptides or a blocking anti-beta1 integrin antibody. VDR expression was also reduced by disruption of the actin cytoskeleton with cytochalasin D. Malignant keratinocytes (SCC12B2 and A431), characterized by, anchorage-independent growth, displayed a profound resistance to suspension-induced suppression of VDR, cyclin D1, and c-myc. Taken together, our results associate VDR expression [and 1,25(OH)2D3 responsiveness] with cell adhesion and an organized cytoskeleton, which are also required for cell growth of primary cells.
ISSN: 0022-202X
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Dermatology
Clinical and Experimental Endocrinology
Laboratory of Dermatoimmunology (+)
× corresponding author
# (joint) last author

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