Vitamin D-1alpha-hydroxylase and vitamin D-24-hydroxylase in benign and malign breast tissue.

摘要

BACKGROUND: It is known that 1,25(OH)2D3 can be metabolized to 1,24(OH)2D3 in breast tissue. This tissue-specific expression of 24-OHase may act as a pivotal link between vitamin D status (25(OH)D3 level) and the anticancer effects of 1,25(OH)2D3. Different expressions of the enzymes of vitamin D metabolism are found in breast cancer cells and tissues, and alternative splicing may play a role in biological functions and may cause tissue-specific variations. We describe the expression of vitamin D-1alpha-hydroxylase and vitamin D-24-hydroxylase in benign and malign breast tissues. We estimated that alternative splicing of the enzymes would lead to a catalytically dysfunctional product and may lead to a lower reduction of the target protein. MATERIAL AND METHODS: Expression of 1alpha-OHase and 24-OHase RNA and protein was assessed using a real-time polymerase chain reaction (RT-PCR) and on protein level by Western blot in benign and malign breast tissue samples. RESULTS: In breast cancer tissue the expression of 1alpha-OHase and 24-OHase were reduced significantly compared to benign breast tissue. CONCLUSION: The results described above do not support results of previous studies. Alternative splicing of 1alpha-OHase and 24-OHase may regulate the levels of active enzyme but is more likely due to different cell types in samples with the result of testing a variety of tissue samples not purified benign and malign breast cancer cells. The significance of smaller variants in cells has not been clarified either, but it is known that they are not able to use 25(OH)D3 as a substrate to generate 1,25(OH),D3.