Effects of phorbol esters on normal and tumorous mouse mammary epithelial cells embedded in collagen gels.
The effects of phorbol esters on mammary epithelial cells from BALB/cfC3H/Crgl "midpregnant mice" (i.e., mice at the midterm of pregnancy) and from mammary adenocarcinomas (also from BALB/cfC3H/Crgl mice) grown in a collagen gel matrix were studied. 12-O-Tetradecanoylphorbol 13-acetate (TPA), when added to the media, caused an increased proliferation of both normal and cancerous mammary epithelial cells in a dose-dependent manner. The degree of enhancement of proliferation by TPA ranged from no increase in cell number at 3% swine serum (SW) concentration to two to three times the number of cells in the control cultures when 10 or 25% SW was used. Optimal growth was obtained with a TPA concentration of 0.1 or 1.0 microgram/ml. Increasing the SW concentration (3, 5, 10, or 25%) enhanced the proliferative effect of TPA. Cholera toxin (0.01 microgram/ml) enhanced the proliferative effect of TPA on normal cells but had a variable effect on tumor cells. The addition of TPA also resulted in a morphologic change in the epithelial colonies from midpregnant mice and from mammary tumors and caused them to assume a fibroblastic appearance. The addition of 4 alpha-phorbol or 4 alpha-phorbol 12,13-didecanoate to mammary epithelial cultures had no proliferative or morphologic effect. The results demonstrate that TPA has a growth-promoting effect on normal and cancerous mouse mammary epithelial cells.
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced*; D002478:Cells, Cultured; D003094:Collagen; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000187:drug effects; D005260:Female; D008321:Mammary Glands, Animal / Q000187:drug effects* / Q000473:pathology; D008325:Mammary Neoplasms, Experimental / Q000473:pathology*; D051379:Mice; D008815:Mice, Inbred Strains; D010703:Phorbol Esters / Q000494:pharmacology*; D010704:Phorbols / Q000494:pharmacology*; D011247:Pregnancy; D013268:Stimulation, Chemical
D010703:Phorbol Esters; D010704:Phorbols; D003094:Collagen