The influence of glucocorticoids on the growth of a human leiomyosarcoma cell line SK-LMS-1.
A cell line derived from a human leiomyosarcoma, SK-LMS-I, has cystolic [Bmax 201.6 +/- 39.7, means +/- SD, fm/mg cytosol protein KD 14.6 +/- 7.8 nM (n = 8)] and nuclear [Bmax 189.2 +/- 87.3 fM/mg DNA, KD 4.8 +/- 0.26 nM (n = 5)] glucocorticoid receptor, by Scatchard analysis of tumors grown in male athymic mice. Tumor growth of SK-LMS-I cells in male athymic mice is inhibited by daily s.c. injection of DEX 5 micrograms, DEX 25 micrograms, DEX 5 micrograms with 5 mu RU-486 and 5 micrograms RU-486. In sharp contrast, in vitro, glucocorticoid markedly stimulates the growth (as determined by cell number) of SK-LMS-I cells, principally at higher cell densities (days 10-21 of growth carried on over a 21- to 23-day period), the greatest stimulation being seen with DEX 10(-6) to 10(-8) M, and no stimulation being seen with DEX 10(-9) and 10(-10) M. In vitro, glucocorticoids with higher affinity for the GR stimulate growth, steroids with lower affinity inhibit growth. No alterations in cell-cycle distribution (percent G0/G1, S, or G2/m) could be found by flow cytometric analysis of glucocorticoid-stimulated asynchronously growing cultures. Single, isolated, untreated SK-LMS-I cells form colonies in soft agar with an efficiency of 1.78 +/- 0.10%. Pre-treatment of cells with DEX 10(-7) M increases this to 3.24 +/- 0.17%, while cells pre-treated with both DEX 10(-7) M RU-486 10(7) M form colonies with the same efficiency as untreated cells. Glucocorticoids have inhibitory effects on in vivo growth and stimulatory effects on in vitro growth of a GR-positive human leiomyosarcoma cell line.
Madsen
W E
WE
Department of Surgery, University of Illinois College of Medicine, Cook County Hospital, Chicago.
Gupta
T K
TK
Walker
M J
MJ
D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D002467:Cell Nucleus / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005938:Glucocorticoids / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007890:Leiomyosarcoma / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D015735:Mifepristone / Q000494:pharmacology; D009368:Neoplasm Transplantation; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D014407:Tumor Cells, Cultured
D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D015735:Mifepristone; D003907:Dexamethasone