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Effects of Host Hormonal Status on Binding of Activated Estrogen Receptor to Nuclei from R3230AC and 7,12-Dimethylbenz[a]anthracene-induced Mammary Tumors¹

Department of Biochemistry and the Cancer Center, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642

The effects of various hormonal perturbations that alter growth of two different rat mammary tumors in vivo were investigated by study of the interactions of [³H]estradiol-charged estrogen receptors ([³H]ER) with tumor nuclei in vitro. Nuclei from the transplantable R3230AC adenocarcinoma were isolated after ovariectomy, estrogen treatment, or progesterone treatment. Saturable specific binding of [³H]ER to nuclei was assayed in this in vivo-like system. Scatchard analysis of [³H]ER-nuclear binding data indicated that these perturbations did not affect affinity, which ranged from K_d 1.0 to 2.4 nM. However, the number of [³H]ER-binding sites/nucleus was altered according to the treatment: intact rats, 94,500 ± 4,200; ovariectomy, 70,400 ± 3,200; ovariectomy plus estradiol, 82,100 ± 5,800; and ovariectomy plus progesterone, 73,900 ± 2,500. Nuclei from primary tumors induced by 7,12-dimethylbenz(a)anthracene displayed similar affinities for [³H]ER, although these tumors had fewer binding sites per nucleus. Animals bearing 7,12-dimethylbenz(a)-anthracene-induced tumors were either ovariectomized or made diabetic by administration of streptozotocin, perturbations that cause regression of the majority of tumors. The number of [³H]ER binding sites per nucleus, in tumors classified according to growth characteristics in host animals subsequent to hormonal perturbation, was: intact growing 36,300 ± 3,400; ovex regressing, 15,400 ± 3,400; over, estrogen-treated growing, 28,100 ± 2,700; diabetic regressing, 19,500 ± 2,400; diabetic static, 32,100 and diabetic growing, 42,000 ± 7,100. These results indicate that (a) the number of nuclear ER-binding sites can be reduced by hormonal interventions that cause tumor regression and (b) endogenous ovarian hormones may play a role in regulating nuclear ER binding.

¹ The work was supported by Grant BC-475 from the American Cancer Society and, in part, by USPHS Grant CA16660.

² Supported by Cancer Research Training Grant T32CA09363.

³ To whom requests for reprints should be addressed, at Department of Biochemistry, P. O. Box 607, The University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Rochester, NY 14642.

Received 7/22/88. Revised 11/22/88. Accepted 11/29/88.