We have examined the ability of co-cultured mouse mammary fat pad (MFP) to modulate the response of mouse mammary epithelial cells to a number of mitogens in vitro. In a series of 4 experiments, COMMA-1D cells were cultured with or without epithelium-free MFP obtained from the abdominal mammary glands of 23-day old virgin, female BALB/c mice. Final cell number was quantified as total DNA after 7 days. The main effect of MFP was significant in all experiments, MFP alone inducing a 6.1 to 8.2-fold increase in cell number relative to basal medium (BM) controls (P<0.001). Furthermore, this stimulatory effect of MFP synergised (P<0.02) with the mitogenic effect of 10% foetal calf serum (FCS). Examination of the response to several mammogenic hormones indicated that insulin (10 ug/ml) alone did not increase cell number (P>0.05), and interacted with the effect of MFP (P<0.001). There was no effect of prolactin (2.5 ug/ml) either alone or with MFP, whereas hydrocortisone (2.5 ug/ml) attenuated the response to MFP (P<0.001). In the absence of MFP, insulin-like growth factor-I (IGF-I; 75 ng/ml) did not increase cell number (P>0.05), whilst epidermal growth factor (EGF; 25 ng/ml) significantly increased cell number 3.7-fold. Both of these growth factors markedly interacted with the effect of MFP (P<0.001). When cultured with the combination of these growth factors and MFP, the final cell number was 29.2 times that of BM alone (25.14 ± 0.84 vs 0.86 ± 0.12 ug DNA/well). There was no effect of prostaglandin E2 (PGE2; 0.5 ug/ml) or indomethacin (5 mg/ml), an inhibitor of prostaglandin synthesis, in the absence or presence of MFP. These findings demonstrate that a diffusible factor(s) from the MFP interacts with several regulators of mammary growth to markedly stimulate epithelial proliferation in vitro. Such a factor appears distinct from a number of classical mitogens, and may be involved in the regulation of mammary development in vivo.

CA, Morris, SR Davis, SJ Eichler, and NG Cullen

Proceedings of the New Zealand Society of Animal Production, Volume 54, , 121-124, 1994
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