This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hissin, P. J. Articles by Hilf, R. Search for Related Content PubMed PubMed Citation Articles by Hissin, P. J. Articles by Hilf, R.

Effects of Estrogen to Alter Amino Acid Transport in R3230AC Mammary Carcinomas and Its Relationship to Insulin Action¹

Biochemistry Department [P. J. H., R. H.] and University of Rochester Cancer Center [R. H.], University of Rochester School of Medicine and Dentistry, Rochester, New York 14642

The effects of estrogens on transport and incorporation of amino acids into the R3230AC mammary adenocarcinoma were studied in vivo and in vitro. Dissociated tumor cells from ovariectomized rats, like those from diabetic rats, displayed elevated transport of proline, representing entry by the A system; transport of phenylalanine (L system) was unaltered, as was glucose transport and its utilization. Administration of estradiol valerate decreased the entry of proline into tumor cells from intact, diabetic, or ovariectomized animals; the response to the steroid hormone was greater in ovariectomized or diabetic rats compared to intact animals. The time course of the effects of estrogen treatment was examined in diabetic rats. By 72 hr, transport of both proline and leucine was significantly decreased; incorporation of leucine into proteins and uridine into RNA was significantly reduced by 24 hr after injection of estradiol valerate. The effects of estrogen in vivo to reduce transport of amino acids and their incorporation into proteins appeared to correlate with the reduced tumor growth observed.

Experiments were performed to examine the effects of 17ß-estradiol in vitro on amino acid transport into dissociated cells from ovariectomized or diabetic rats. Under these experimental conditions, 17ß-estradiol (10^-6 M) inhibited proline transport with little or no effect on leucine transport in cells from ovariectomized rats; in cells from diabetic rats, proline transport and leucine incorporation were significantly reduced by estradiol, whereas phenylalanine transport was slightly inhibited (20%). The effect of estradiol in vitro was also manifest in tumor cells obtained from diabetic rats treated in vivo with estradiol valerate; estradiol in vitro caused a further reduction in proline transport but not in leucine transport, results that imply some specificity to the action of estrogen on the A system.

Since we had earlier shown that insulin action on transport in these tumor cells was directed towards the A system, we examined the effects of insulin, estradiol, and their combination in vitro on proline and leucine transport. Insulin (10^-8 M) stimulated proline transport; 17ß-estradiol, at a selected lower level of 10^-8 M, inhibited proline transport. When both were added in vitro, estradiol (10^-8 M) was capable of significantly reducing the insulin (10^-8 M)-induced increase in proline transport. Leucine transport was not altered in any of these experiments. Together, these data suggest that estrogens are capable of inhibiting amino acid transport into the R3230AC mammary carcinoma, an effect that is compatible with reduced tumor growth. The possible relationship of estrogen and insulin at the level of amino acid transport remains to be elucidated.

¹ Supported by USPHS Grant CA 16660 and, in part, by Cancer Center Core Support CA Grant 5-P30-CA 11198-09, National Cancer Institute, NIH.

² Submitted in partial fulfillment of the requirements for the Ph.D. degree. Present address: Department of Health, Education, and Welfare, Section of Cellular Metabolism and Obesity, DANAC Building #4, National Institute of Arthritis, Metabolism, and Digestive Diseases, Bethesda, Md. 20205.

³ To whom requests for reprints should be addressed.

Received 1/30/79. Accepted 5/31/79.

This article has been cited by other articles:

				J. T. Dever and A. A. Elfarra L-Methionine Toxicity in Freshly Isolated Mouse Hepatocytes Is Gender-Dependent and Mediated in Part by Transamination J. Pharmacol. Exp. Ther., September 1, 2008; 326(3): 809 - 817. [Abstract] [Full Text] [PDF]