Receptors for insulin and estradiol and transport of selected amino acids were examined in two rodent mammary tumor models. Carcinomas induced by 7,12-dimethylbenz(a)anthracene are hormone dependent, and the majority regress in diabetic or ovariectomized hosts; in the former insulin binding was increased and estrogen receptor decreased, whereas in the latter insulin binding was decreased. Insulin treatment of diabetic tumor-bearing animals usually reactivated tumor growth, and this was accompanied by an increased estrogen-binding capacity. The R3230AC mammary adenocarcinoma, a transplantable hormone-responsive tumor, grows faster in diabetic hosts and is inhibited by insulin therapy. Tumors from diabetic animals display higher insulin binding and reduced estrogen receptor. Ovariectomy resulted in a greater than 2-fold elevation in insulin binding in the R3230AC tumor, and estrogen treatment reduced insulin binding. In short-term tissue culture of R3230AC cells, estradiol in vitro appeared to decrease insulin binding and insulin increased estrogen-binding capacity.

Enzymatically dissociated R3230AC tumor cells were used for characterization of carrier-mediated transport of various substrates. Entry of glucose, proline, or phenylalanine demonstrated characteristics similar to those of normal cells. However, with α-aminoisobutyric acid, both Na+-independent and Na+-dependent carrier-mediated entry was observed, suggesting that this analog entered these tumor cells by more than one system. Cells from R3230AC tumors obtained from diabetic hosts showed increased entry of proline or α-aminoisobutyric acid; insulin treatment of diabetic rats returned the rate of entry of these substrates to levels seen in tumor cells from intact rats. Phenylalanine entry was not affected by alteration of the insulin level of the host, indicating that the effects of insulin are specific. Preliminary results showed that estrogen therapy reduced entry of proline and leucine. Thus, entry of proline in vitro could be related to the effects of hormones on growth behavior of the tumor in vivo, and further investigation could provide a better understanding of these hormonal interrelationships at the cellular level.

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Presented at the John E. Fogarty International Center Conference on Hormones and Cancer, March 29 to 31, 1978, Bethesda, Md. Supported by USPHS Grants CA 16660 and CA 11198 from the National Cancer Institute, NIH.

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