Correlation between induction of the mac25 gene and anti-proliferative effects of 1α,25(OH)2-D3 on breast cancer and leukemic cells

In the differentiation of a myelomonocytic cell line U937 treated with 1α,25-dihydroxyvitamin D3 [1α,25(OH)2-D3], transient proliferation was observed prior to cell growth arrest. The expression of the p21 and p27 genes increased transiently and decreased quickly in the proliferation, suggesting that other genes may contribute to the growth arrest of the cell line after reduction of the p21 and p27 genes. The mac25 gene was isolated as a gene associated with cellular senescence and growth suppression. Despite a previous report that retinoic acid (RA) induced the mac25 gene, the mac25 gene did not increase in U937 cells treated with RA but did increase in the cells treated with 1α,25(OH)2-D3. The high level of the expression of the mac25 gene was detected for four days after the 1α,25(OH)2-D3 treatment. Therefore, mac25 may contribute to the growth arrest of U937 cells treated with 1,25-D3. The growth responses to 1α,25(OH)2-D3 and the expression of the mac25 gene of three other cancer cell lines (Saos-2, U2OS and MCF7) were studied. Although the growth suppression was observed in MCF7 cells treated with 1α,25(OH)2-D3 dose-dependently (1-100 nM of 1α,25(OH)2-D3), the treatment of 100 nM of 1α,25(OH)2-D3 had no effect on the growth of Saos-2 and U2OS cells. The expression of the mac25 gene was up-regulated in MCF7 cells treated with 100 nM of 1α,25(OH)2-D3, whereas no transcript of the mac25 gene was detected in Saos-2 and U2OS cells even when they were treated with 100 nM of 1α,25(OH)2-D3. These results suggest that the cellular response to 1α,25(OH)2-D3 may depend on the induction of the mac25 gene.