Specific stimulation by estradiol of tissue-type plasminogen activator production in 7,12-dimethylbenz[a]anthracene-induced rat mammary tumor cells.
The hormonal regulation of two plasminogen activators, tissue-type plasminogen activator (t-PA) and urokinase (u-PA), was studied both in 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat mammary carcinoma and in DMBA-induced rat mammary dysplasia. t-PA activity in DMBA-mammary carcinoma was decreased markedly by oophorectomy and recovered upon estradiol administration to reach the maximum level at 12 hr. In contrast to its effect on DMBA-mammary carcinoma, estradiol had no effect on t-PA activity in DMBA-mammary dysplasia. Furthermore, DMBA-mammary carcinoma cells in primary culture displayed similar estrogen-dependency in production of t-PA, while t-PA production in DMBA-mammary dysplasia cells was not under the control of estradiol in vitro. Moreover, estrogen-stimulated production of u-PA activity was not observed in DMBA-mammary carcinoma cells or DMBA-mammary dysplasia cells both in vivo and in vitro. Taken together, these results suggest that estrogen stimulates the production of t-PA but not u-PA and that this estrogen dependency of t-PA is limited to malignant DMBA-mammary tumor cells.
Yamashita
J
J
Department of Surgery II, Kumamoto University Medical School, Japan.
Inada
K
K
Yamashita
S
S
Matsuo
S
S
Nakashima
Y
Y
Ogawa
M
M
D015127:9,10-Dimethyl-1,2-benzanthracene; D000595:Amino Acid Sequence; D000818:Animals; D004790:Enzyme Induction / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005348:Fibrocystic Breast Disease / Q000201:enzymology; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000201:enzymology*; D008969:Molecular Sequence Data; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D010959:Tissue Plasminogen Activator / Q000096:biosynthesis*; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis
D004958:Estradiol; D015127:9,10-Dimethyl-1,2-benzanthracene; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator