THE PROLIFERATION OF MOUSE MAMMARY EPITHELIAL-CELLS IN RESPONSE TO SPECIFIC MITOGENS IS MODULATED BY THE MAMMARY FAT PAD IN-VITRO

The ability of the murine mammary fat pad to directly stimulate the gr owth of mammary epithelial cells and to modulate the effects of variou s mammogenic agents has been investigated in a newly described, hormon e-and serum-free coculture system. COMMA-1D mouse mammary epithelial c ells were cultured for 5 or 7 d with various supplements in the absenc e or presence of epithelium-free mammary fat pad explants from virgin female BALB/c mice. Cocultured fat pad stimulated increases in the DNA content of COMMA-1D cultures by two-to threefold or six-to eightfold after 5 or 7 d, respectively. The mitogenic effect was additive to tha t of 10% fetal calf serum and could not be attributed to the release o f prostaglandin E-2 or synthesis of prostaglandins by epithelial cells . In addition, bovine serum albumin attenuated (P < 0.05) the mitogeni c effect of cocultured mammary fat pad. Added alone, insulinlike growt h factor-I, epidermal growth factor, and insulin increased (P < 0.05) total DNA of COMMA-1D cultures by 2.5-, 3.7-, and 2.3-fold, respective ly. Cocultured mammary fat pad markedly interacted (P < 0.01) with the se mitogens to yield final DNA values that were 21.2-, 13.3-, and 22.1 -fold greater than in basal medium only. Associated with this prolifer ation was the formation of numerous domes above the COMMA-1D monolayer . There was no proliferative response to growth hormone or prolactin i n the absence or presence of cocultured fat pad (P > 0.05). Whereas hy drocortisone did not alter cell number, it attenuated (P < 0.05) the m itogenic effect of cocultured mammary fat pad. These results indicate that the murine mammary fat pad is not only a direct source of mitogen ic activity, but also modulates the response of mammary epithelial cel ls to certain mammogens.