Cordes T, Fischer D, Thill M, Becker S, Friedrich M, Salehin D
Clinic for Obstetrics and Gynecology, University of Schleswig-Holstein, Campus Lübeck, Lübeck, Germany.
Eur J Gynaecol Oncol. 2010;31(2):151-5.
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.
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.
In breast cancer tissue the expression of 1alpha-OHase and 24-OHase were reduced significantly compared to benign breast tissue.
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.
已知1,25(OH)₂D₃可在乳腺组织中代谢为1,24(OH)₂D₃。24-羟化酶的这种组织特异性表达可能是维生素D状态（25(OH)D₃水平）与1,25(OH)₂D₃抗癌作用之间的关键环节。在乳腺癌细胞和组织中发现了维生素D代谢酶的不同表达，可变剪接可能在生物学功能中起作用，并可能导致组织特异性差异。我们描述了维生素D-1α-羟化酶和维生素D-24-羟化酶在良性和恶性乳腺组织中的表达。我们估计这些酶的可变剪接会导致催化功能失调的产物，并可能导致靶蛋白的减少降低。
使用实时聚合酶链反应（RT-PCR）评估良性和恶性乳腺组织样本中1α-羟化酶和24-羟化酶RNA及蛋白质的表达，并通过蛋白质印迹法评估蛋白质水平。
与良性乳腺组织相比，乳腺癌组织中1α-羟化酶和24-羟化酶的表达显著降低。
上述结果不支持先前研究的结果。1α-羟化酶和24-羟化酶的可变剪接可能调节活性酶的水平，但更可能是由于样本中细胞类型不同，结果是检测了多种未纯化的良性和恶性乳腺癌细胞的组织样本。细胞中较小变体的意义也尚未阐明，但已知它们不能将25(OH)D₃用作底物来生成1,25(OH)₂D₃。
