ESTROGEN-DEPENDENT PLASMINOGEN-ACTIVATOR IN 7,12-DIMETHYLBENZ-[A]ANTHRACENE-INDUCED RAT MAMMARY-TUMORS INVIVO AND INVITRO

  • 1 January 1984
    • journal article
    • research article
    • Vol. 75  (8) , 681-689
Abstract
Hormonal regulation of plasminogen activator in rat mammary tumor induced by 7,12-dimethylbenz[.alpha.]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 h. This estrogen-stimulated production of the enzyme was prevented by actinomycin D, cycloheximide, and tamoxifen [an antiestrogen drug], indicating that in DMBA-tumor, estrogen might regulate de novo synthesis of plasminogen activator at a transcriptional level via an estrogen receptor system. DMBA-tumor cells in primary culture displayed similar estrogen-dependency toward the production of the enzyme without any cell proliferation. The action of estrogen apparently is mediated neither by cell division nor by prolactin, another hormone postulated to be responsible for the development and growth of DMBA-tumor. The primary function of estrogen could be to induce plasminogen activator, which is probably essential to maintain the malignant state of DMBA-tumor.