Effect of estrone on the growth of 7,12-dimethylbenz(a)anthracene-induced mammary carcinoma in the rat: a model of postmenopausal breast cancer.
Estradiol (E2) is well known as stimulator of the growth of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary tumors. The effect of estrone (E1), however, has not been described in this model of human breast cancer. As E1 is the predominant estrogen precursor in postmenopausal women, we have investigated the effect of this steroid and, simultaneously, the potential role of the enzyme required for interconversion of the weak estrogen E1 into the potent estrogen E2, namely 17 beta-hydroxysteroid dehydrogenase, in the growth of DMBA-induced mammary carcinoma in the rat. Treatment for 20 days of ovariectomized animals bearing DMBA-induced mammary tumors with twice daily doses of 0.375, 0.75, 1.5, and 3.0 micrograms E1 increased total tumor area by 48%, 101%, 116%, and 129%, respectively. Treatment with the highest dose of E1 increased progesterone receptor levels by 20.4- and 2.3-fold in the DMBA-induced tumors and uterus, respectively. After treatment with E1, the concentration of this steroid was similar in the serum and tumor tissue, whereas concentrations of E2 were approximately 3-fold higher in the tumor tissue compared to serum. Treatment with a 1.0-microgram dose of E1 caused a 60% increase in tumoral 17 beta-hydroxysteroid dehydrogenase activity in ovariectomized animals, thus favoring E2 formation from E1 in tumors. In addition, treatment with the 1.0-microgram dose of E1 or 0.1 microgram E2 gave similar stimulatory effects on tumor growth and uterine weight in ovariectomized animals; the values were comparable to those found in intact animals. The present data indicate that ovariectomized rats bearing DMBA-induced mammary tumors and treated with E1 can be a useful model of postmenopausal breast cancer.
Li
S
S
Medical Research Council Group in Molecular Endocrinology, CHUL Research Center, Montreal, Quebec, Canada.
Martel
C
C
Dauvois
S
S
Bélanger
A
A
Labrie
F
F
D015067:17-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D004195:Disease Models, Animal; D004958:Estradiol / Q000494:pharmacology; D004970:Estrone / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000737:chemistry / Q000473:pathology*; D010052:Ovariectomy; D017698:Postmenopause; D051381:Rats; D017207:Rats, Sprague-Dawley; D011980:Receptors, Progesterone / Q000032:analysis
D011980:Receptors, Progesterone; D004970:Estrone; D004958:Estradiol; D015127:9,10-Dimethyl-1,2-benzanthracene; D015067:17-Hydroxysteroid Dehydrogenases