INDUCTION OF APOPTOSIS IN ANDROGEN-INDEPENDENT MOUSE MAMMARY CELL-LINE BY 1,25-DIHYDROXYVITAMIN D-3

Androgen-dependent tumors eventually progress to independent tumors af ter androgen withdrawal. Effective treatment for hormone-independent t umors is therefore needed. Androgen-independent CS-2 cells could grow in serum-free culture whether androgen is present in the medium or not . In the present study, the mechanism of cell death in CS-2 cells was examined after 1, 25-dihydroxyvitamin D-3 [1, 25(OH)(2)D-3] treatment. 1, 25(OH)(2)D-3 has been examined as an anti-tumor agent, but its rol e in promoting cell death is poorly understood. based upon the tempora l sequence of DNA fragmentation, morphologic changes and loss of cell viability, the cells underwent apoptosis with 1, 25(OH)(2)D-3 treatmen t. Northern-blot analysis was used to identify a series of genes whose expression per cell is enhanced during the apoptotic pathway, In the apoptotic process induced by 1, 25(OH)(2)D-3, mRNA expression of testo sterone-repressed prostatic message 2, transforming growth factor beta 1, glucose-regulated 78-kDa protein and calmodulin increased. Flow-cy tometric analysis showed that 1, 25(OH)2D, treatment resulted in a blo ck in G(0)/G(1) of the cell cycle. These results demonstrate that andr ogen-independent CS-2 cells retain the ability to undergo apoptosis by 1, 25(OH)(2)D-3. This system appears to be a good model for investiga ting apoptosis of hormone-independent cancer. (C) 1996 Wiley-Liss, Inc .