Vanoirbeek Els, Eelen Guy, Verlinden Lieve, Marchal Kathleen, Engelen Kristof, De Moor Bart, Beullens Ine, Marcelis Suzanne, De Clercq Pierre, Bouillon Roger, Verstuyf Annemieke
Laboratorium voor Experimentele Geneeskunde en Endocrinologie, Katholieke Universiteit Leuven, Gasthuisberg, 3000 Leuven, Belgium.
Anticancer Res. 2009 Sep;29(9):3585-90.
1alpha,25-Dihydroxyvitamin D3 [1,25-(OH)2D3] is the biological active form of vitamin D. Its antiproliferative capacities make it a potential drug to treat diseases such as cancer. The clinical use of 1,25-(OH)2D3 as an antiproliferative agent is hampered by its calcemic effects. Hence, structural analogs such as the seco-9,11-bisnor-17-methyl analog, WY1112, have been developed with superagonistic capacities. This study aims to distinct the molecular activities of 1,25-(OH)2D3 and WY1112 and identify possible differences in gene expression.
Total RNA was extracted from MCF-7 breast cancer cells treated with 1,25-(OH)2D3 or WY1112 and was used for microarray analysis.
The experiments revealed that WY1112 induces the same genes as 1,25-(OH)2D3, but the induction level of the individual genes is higher. Microarray analysis did not reveal genes that were exclusively regulated by WY1112.
The superagonistic vitamin D analog WY1112 induces the same set of genes as 1,25-(OH)2D3, but the level of induction of the individual genes is higher.
1α,25 - 二羟基维生素D3 [1,25-(OH)2D3]是维生素D的生物活性形式。其抗增殖能力使其成为治疗癌症等疾病的潜在药物。1,25-(OH)2D3作为抗增殖剂的临床应用受到其血钙效应的阻碍。因此，已开发出具有超激动能力的结构类似物，如9,11 - 二去甲 - 17 - 甲基类似物WY1112。本研究旨在区分1,25-(OH)2D3和WY1112的分子活性，并确定基因表达中可能存在的差异。
从用1,25-(OH)2D3或WY1112处理的MCF - 7乳腺癌细胞中提取总RNA，并用于微阵列分析。
实验表明，WY1112诱导的基因与1,25-(OH)2D3相同，但各个基因的诱导水平更高。微阵列分析未发现仅由WY1112调控的基因。
超激动性维生素D类似物WY1112诱导的基因集与1,25-(OH)2D3相同，但各个基因的诱导水平更高。
