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

Int J Mol Med. 2001 May;7(5):515-20. doi: 10.3892/ijmm.7.5.515.


In the differentiation of a myelomonocytic cell line U937 treated with 1alpha,25-dihydroxyvitamin D3 [1alpha,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 1alpha,25(OH)2-D3. The high level of the expression of the mac25 gene was detected for four days after the 1alpha,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 1alpha,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 1alpha,25(OH)2-D3 dose-dependently (1-100 nM of 1alpha,25(OH)2-D3), the treatment of 100 nM of 1alpha,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 1alpha,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 1alpha,25(OH)2-D3. These results suggest that the cellular response to 1alpha,25(OH)2-D3 may depend on the induction of the mac25 gene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Northern
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Calcitriol / pharmacology*
  • Carrier Proteins / genetics*
  • Cell Cycle Proteins*
  • Cell Division / drug effects*
  • Cell Line
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclin-Dependent Kinase Inhibitor p27
  • Cyclins / genetics
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation / drug effects
  • Humans
  • Insulin-Like Growth Factor Binding Proteins*
  • Leukemia / drug therapy
  • Leukemia / genetics*
  • Leukemia / pathology
  • Microtubule-Associated Proteins / genetics
  • RNA / drug effects
  • RNA / genetics
  • RNA / metabolism
  • Time Factors
  • Tumor Cells, Cultured
  • Tumor Suppressor Proteins*
  • U937 Cells


  • CDKN1A protein, human
  • Carrier Proteins
  • Cell Cycle Proteins
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Insulin-Like Growth Factor Binding Proteins
  • Microtubule-Associated Proteins
  • Tumor Suppressor Proteins
  • insulin-like growth factor binding protein-related protein 1
  • Cyclin-Dependent Kinase Inhibitor p27
  • RNA
  • Calcitriol