Reduction of proline transport in R3230AC mammary carcinomas by estrogens in vitro.
The effects of estrogens on proline and leucine transport into enzymatically dissociated cells from the R3230AC mammary adenocarcinoma were studied. Estradiol-17beta demonstrated a time- and dose-dependent reduction of proline transport; at 10-6M, transport of proline was decreased by 50 percent. Kinetic analysis of these effects indicate that estradiol displayed characteristics of a non-competitive inhibitor, with a Ki of 1.79 microM. Other estrogens, and the anti-estrogen tamoxifen, gave somewhat higher estimated Ki values and could be ranked as inhibitors as follows estradiol 17beta greater than diethylstilbestrol greater than tamoxifen greater than estriol congruent to estrone greater than estradiol-17alpha. No effects of these estrogens on leucine transport were observed, indicating their selectiveness for the A system. The synthetic glucocorticoid, dexamethasone, was comparable to diethylstilbestrol as an inhibitors of proline transport, but dexamethasone also decreased transport of leucine, Testosterone and progesterone were approximately comparable to estrone in their actions. It is proposed that these actions of estrogens represent one potential mechanism whereby pharmacological levels exert therapeutic benefit in the treatment of advanced breast cancer.
D000230:Adenocarcinoma / Q000378:metabolism*; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology; D004054:Diethylstilbestrol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D007700:Kinetics; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism*; D011392:Proline / Q000378:metabolism*; D051381:Rats; D013629:Tamoxifen / Q000494:pharmacology
D004967:Estrogens; D013629:Tamoxifen; D004958:Estradiol; D004054:Diethylstilbestrol; D003907:Dexamethasone; D011392:Proline