Analysis of the vitamin D system in basal cell carcinomas (BCCs)

Abstract

Using real-time PCR (LightCycler) and immunohistochemistry, we have analyzed expression of key components of the vitamin D system in basal cell carcinomas (BCCs) and normal human skin (NS).

Increased VDR-immunoreactivity was demonstrated in BCCs using a streptavidin-peroxidase technique.

RNA expression of vitamin D receptor (VDR) and of main enzymes involved in synthesis and metabolism of calcitriol (vitamin D-25-hydroxylase [25-OHase], 25-hydroxyvitamin D-1alpha-hydroxylase [1alpha-OHase], 1,25-dihydroxyvitamin D-24-hydroxylase [24-OHase]) was detected in BCCs and NS.

Expression levels were determined as ratios between target genes (VDR, 1alpha-OHase, 25-OHase, 24-OHase) and the housekeeping gene glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as internal control. Median of mRNA ratios for VDR/GAPDH (BCCs: 16.54; NS: 0.00021), 1alpha-OHase/GAPDH (BCCs: 0.739; NS 0.000803) and 24-OHase/GAPDH (BCCs: 0.00585; NS 0.000000366) was significantly (Wilcoxon-Mann-Whitney U-test) elevated in BCCs. In contrast, median of mRNA ratio for 25-OHase/GAPDH (BCCs: 0.17; NS: 0.016) was not significantly altered in BCCs as compared to NS.

Additionally, we report for the first time expression of 1alpha-OHase splice variants in BCCs and NS, that were detected using conventional RT-PCR.

In conclusion, our findings provide supportive evidence for the concept that endogeneous synthesis and metabolism of vitamin D metabolites as well as VDR expression may regulate growth characteristics of BCCs.

New vitamin D analogs that exert little calcemic side effects, their precursors, or inhibitors of 24-OHase may offer a new approach for the prevention or therapy of BCCs. The function of alternative transcripts of 1alpha-OHase that we describe here for the first time in BCCs and NS and their effect on activity level has to be investigated in future experiments.

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