Estrogen-dependent plasminogen activator in 7,12-dimethylbenz[a]anthracene-induced rat mammary tumors in vivo and in vitro.
Hormonal regulation of plasminogen activator in rat mammary tumor induced by 7,12-dimethylbenz[a]anthracene (DMBA) was studied both in vivo and in vitro. Plasminogen activator activity in DMBA-induced tumor (DMBA-tumor) was markedly decreased by ovariectomy, and recovered in a dose-dependent fashion upon estradiol administration, reaching a maximal level at 12 hr. This estrogen-stimulated production of the enzyme was prevented by actinomycin D, cycloheximide, and tamoxifen, indicating that in DMBA-tumor, estrogen might regulate de novo synthesis of plasminogen activator at a transcriptional level via an estrogen receptor system. Furthermore, DMBA-tumor cells in primary culture displayed similar estrogen-dependency toward the production of the enzyme without any cell proliferation. This indicates that the action of estrogen is mediated neither by cell division nor by prolactin, another hormone pastulated to be responsible for the development and growth of DMBA-tumor. Taken together, the present results have led to support the view that the primary function of estrogen is to induce plasminogen activator, which is probably essential to maintain the malignant state of DMBA-tumor.
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D002369:Castration; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000201:enzymology*; D010960:Plasminogen Activators / Q000032:analysis* / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains
D004967:Estrogens; D003609:Dactinomycin; D015127:9,10-Dimethyl-1,2-benzanthracene; D003513:Cycloheximide; D010960:Plasminogen Activators