title: The proliferation of mouse mammary epithelial cells in response to specific mitogens is modulated by the mammary fat pad in vitro.
abstract: The ability of the murine mammary fat pad to directly stimulate the growth of mammary epithelial cells and to modulate the effects of various mammogenic agents has been investigated in a newly described, hormone- and serum-free coculture system. COMMA-1D mouse mammary epithelial cells were cultured for 5 or 7 d with various supplements in the absence 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 that of 10% fetal calf serum and could not be attributed to the release of prostaglandin E2 or synthesis of prostaglandins by epithelial cells. In addition, bovine serum albumin attenuated (P < 0.05) the mitogenic effect of cocultured mammary fat pad. Added alone, insulinlike growth 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, respectively. Cocultured mammary fat pad markedly interacted (P < 0.01) with these 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 proliferation was the formation of numerous domes above the COMMA-1D monolayer. There was no proliferative response to growth hormone or prolactin in the absence or presence of cocultured fat pad (P > 0.05). Whereas hydrocortisone did not alter cell number, it attenuated (P < 0.05) the mitogenic effect of cocultured mammary fat pad. These results indicate that the murine mammary fat pad is not only a direct source of mitogenic activity, but also modulates the response of mammary epithelial cells to certain mammogens.
authors.affiliation: Dairy Science Group, AgResearch, Ruakura Research Centre, Hamilton, New Zealand.
authors.forename: R C
authors.initials: RC
authors.lastname: Hovey
authors.forename: D D
authors.initials: DD
authors.lastname: MacKenzie
authors.forename: T B
authors.initials: TB
authors.lastname: McFadden
mesh_terms: D000273:Adipose Tissue / Q000502:physiology*; D000818:Animals; D001798:Blood Proteins / Q000494:pharmacology; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D018920:Coculture Techniques / Q000379:methods; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects*; D005260:Female; D008321:Mammary Glands, Animal / Q000166:cytology* / Q000187:drug effects*; D051379:Mice; D008934:Mitogens / Q000494:pharmacology*; D012710:Serum Albumin, Bovine / Q000494:pharmacology
chemical_list: D001798:Blood Proteins; D008934:Mitogens; D012710:Serum Albumin, Bovine