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 Google Scholar Google Scholar Articles by Manni, A. Articles by Bartholomew, M. Search for Related Content PubMed PubMed Citation Articles by Manni, A. Articles by Bartholomew, M.

Polyamines and Autocrine Control of N-Nitrosomethylurea-induced Rat Mammary Tumor Growth in Vitro by Progesterone¹

Departments of Medicine, Pathology, and Behavioral Sciences, The Milton S. Hershey Medical Center, The Pennsylvania State University, Hershey, Pennsylvania 17033

These experiments were designed to test whether autocrine/paracrine mechanisms are involved in the growth-promoting action of progesterone (Pg) in the N-nitrosomethylurea-induced rat mammary tumor cultured in vitro in soft agar clonogenic assay. In support of our hypothesis, we observed that conditioned media obtained from Pg-treated tumors (Pg-CM), consistently stimulated colony formation in our system to the same degree as Pg itself (approximately 140% of control). Treatment with heat, trypsin, and concanavalin A abolished the colony-stimulating effect of Pg-CM, thus suggesting the possible glycoprotein nature of the Pg-inducible growth factor(s). The growth-promoting action of Pg-CM was rather specific since CMs obtained from tumors exposed to a variety of other steroid hormones rarely stimulated colony formation and usually only to a modest degree. Administration of the polyamine biosynthetic inhibitor, -difluoromethylornithine, abolished the colony-stimulating effect of Pg-CM. The inhibitory effect of -difluoromethylornithine was reversed in a dose-dependent fashion by exogenous administration of spermidine, which entirely restored the growth-promoting action of Pg-CM. Addition of increasing amounts of spermidine, however, did not potentiate Pg-CM action under our experimental conditions. Our results indicate that autocrine/paracrine mechanisms may mediate, at least in part, the colony-stimulating effect of Pg in our system. The polyamine pathway plays an essential role in the expression of such control of tumor growth by Pg.

¹ Supported in part by a grant received from the National Cancer Institute, PO1 CA 40011.

² To whom requests for reprints should be addressed, at Division of Endocrinology, The Milton S. Hershey Medical Center, The Pennsylvania State University, Hershey, PA 17033.

Received 10/21/87. Revised 1/19/88. Accepted 1/28/88.