Vanadate enhances the stimulatory action of insulin on DNA synthesis in cultured mouse mammary gland.

In order to assess the importance of ions in the regulation of mammary epithelial cell proliferation, the effect of various polyvalent ions was examined on insulin- and lithium-ion-dependent DNA synthesis in mouse mammary gland from virgin mice cultured in a serum-free, chemically defined medium. Addition of 2 to 10 microM orthovanadate enhanced the stimulatory effect of insulin on DNA synthesis in cultured tissue. Similar results were obtained with metavanadate. In contrast, vanadate did not augment Li+-stimulated DNA synthesis but rather inhibited this process. Vanadate by itself caused only a slight stimulation of DNA synthesis. These results indicate that vanadate acts as a co-mitogen in insulin-stimulated DNA synthesis in cultured mammary cells and suggest that the mitogenic action of insulin involves an ion-dependent path which may be common to the actions of vanadate and lithium ion.