Analysis of the vitamin D system in cutaneous malignancies.
1,25-dihydroxyvitamin D3, the biological active metabolite of vitamin D, has great impact on keratinocyte growth and differentiation, and consequently has already been successfully used in the therapy of hyperproliferative skin disorders. We have now characterized the key components of the vitamin D system (VDR, 1alpha-OHase, 24-OHase and 25-OHase) in cutaneous basal cell carcinomas (BCC) and squamous cell carcinomas (SCC), using immunohistochemical and quantitative real-time PCR techniques. Additionally, proliferative activity (Ki-67 expression), differentiation status (cytokeratin 10 and transglutaminase K expression), rate of apoptosis (TUNEL assay) and the abundance of the main heterodimerization partners of VDR (RXRs) was determined for these tumours and correlated with the components of the Vitamin D system. Our findings indicate that the Vitamin D system may be of high importance for the growth behaviour of BCCs and SCCs and that new vitamin D analogues that exert less calcaemic side effects may be effective in the prevention or treatment of these tumours.
Kamradt
Jörn
J
Department of Dermatology, University of Saarland, Kirrberger Str., 66421 Homburg/Saar, Germany.
Rafi
Leyla
L
Mitschele
Tanja
T
Meineke
Viktor
V
Gärtner
Barbara C
BC
Wolfgang
Tilgen
T
Holick
Michael F
MF
Reichrath
Jörg
J
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism*; D002280:Basal Cell Carcinoma / Q000201:enzymology* / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000235:genetics; D016022:Case-Control Studies; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers / Q000737:chemistry; D015870:Gene Expression; D006801:Humans; D007124:Immunoenzyme Techniques; D020287:In Situ Nick-End Labeling; D019394:Ki-67 Antigen / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism; D012878:Skin Neoplasms / Q000201:enzymology* / Q000235:genetics; D013250:Steroid Hydroxylases / Q000235:genetics / Q000378:metabolism*; D011503:Transglutaminases / Q000032:analysis; D065668:Vitamin D3 24-Hydroxylase
D017931:DNA Primers; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D018167:Receptors, Calcitriol; D018168:Receptors, Retinoic Acid; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D011503:Transglutaminases