RELATIONSHIP BETWEEN INSULIN AND ESTROGEN BINDING TO GROWTH RESPONSE IN 7,12-DIMETHYLBENZ(A)ANTHRACENE-INDUCED RAT MAMMARY-TUMORS

Abstract

Insulin and estrogen binding were determined in 7,12-dimethylbenz(a)anthracene-induced mammary tumors of rats in various endocrine states. Hormonal therapy, such as diabetes and ovariectomy, resulted in differential effects on growth patterns and hormone binding of tumors coexisting in the same or different hosts. Tumors that continued to grow after the host was made diabetic (insulin independent) or started to regress after ovariectomy (ovarian dependent) demonstrated decreased insulin binding. Tumors that regressed in diabetic hosts (insulin dependent) or continued to grow in ovariectomized animals (ovarian independent) showed an increased insulin-binding capacity. No significant change in insulin binding was observed in tumors that remained static after ovariectomy or induction of diabetes. Estrogen binding in tumor cells from diabetic rats paralleled the pattern of tumor growth response to diabetes; insulin-independent tumors demonstrated a significant increase in binding compared to tumors from intact hosts, and insulin-dependent tumors showed decreased estrogen receptor levels. Insulin plays a positive role in regulating estrogen-binding capacity; ovarian hormones may play a role in regulating insulin-binding capacity and a relationship between insulin and ovarian hormones and the growth of 7,12-dimethylbenz(a)anthracene-induced tumors is suggested and may have therapeutic implications.