[Stimulation and inhibition of the growth of sex-steroid-dependent tumors].
Shionogi carcinoma 115 (SC 115) has been accepted for 20 years as a model androgen-dependent mouse mammary tumor. However, we recently found that the growth of SC 115 in vivo is also stimulated by large doses of estrogen via the estrogen receptor. In the present study, the action mechanisms involved in the growth stimulation of SC 115 were examined using a cloned cell line (SC-3) derived from the SC 115 tumor. In serum-supplemented (2% steroid-free FCS-MEM) and serum-free [HAM F-12: MEM (1:1, v/v) containing 0.1% BSA] media, testosterone (Test, 10(-9)-10(-6) M) markedly increased both the cell number and DNA synthesis of SC-3 cells (by up to 10-fold), whereas estradiol-17 beta (10(-12)-10(-6) M) had no such effects; the Test-induced growth was completely inhibited by the addition of a 100-fold excess of cyproterone acetate (CA). The serum-free medium cultured with SC-3 cells in the presence or absence of 10(-8) M Test was collected [conditioned medium (CM) or conditioned medium without Test (CM-)], and then Test in CM was inactivated by the addition of a 100-fold excess of CA. In the serum-free culture system, the addition of CM without Test activity significantly enhanced the proliferation of SC-3 cells, whereas CM (-) had no such effect. The present findings suggest that the growth-stimulatory activities of androgen and high doses of estrogen on SC 115 cells are mediated by growth factor (s), secreted from SC 115 cells via the androgen receptor and from some of the non-transformed cells via the estrogen receptor, respectively.
D000728:Androgens / Q000502:physiology*; D000818:Animals; D002369:Castration; D002460:Cell Line; D002478:Cells, Cultured; D003520:Cyclophosphamide / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D006133:Growth Substances / Q000502:physiology; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology*; D051379:Mice; D009368:Neoplasm Transplantation; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000473:pathology*; D013739:Testosterone / Q000494:pharmacology
D000728:Androgens; D004967:Estrogens; D006133:Growth Substances; D013739:Testosterone; D003520:Cyclophosphamide