Rc. Hovey et al., THE PROLIFERATION OF MOUSE MAMMARY EPITHELIAL-CELLS IN RESPONSE TO SPECIFIC MITOGENS IS MODULATED BY THE MAMMARY FAT PAD IN-VITRO, In vitro cellular & developmental biology. Animal, 34(5), 1998, pp. 385-392
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.