Biological effects of glucocorticoid hormones on two rat colon adenocarcinoma cell lines.
Glucocorticoid hormones are thought to play a role in carcinogenesis as they regulate cell differentiation and proliferation. We have investigated the effect of dexamethasone on two cell lines derived from a colon carcinoma, which differ by their tumorigenicity. Dexamethasone was found to inhibit growth of both the progressive (PROb) and the regressive clone (REGb). Upon glucocorticoid treatment, PROb cells were found to secrete an additional Mr approximately 40,000 protein. The synthesis and the release in the culture medium of this protein is stimulated specifically by glucocorticoid agonists, and not by other steroid hormones. The anti-glucocorticoid RU 38486 is inefficient and suppresses the induction of this protein by dexamethasone. Induction is sensitive to actinomycin D, suggesting that regulation may be related to an alteration of the rate of mRNA synthesis. The cellular effect of glucocorticoid hormones being mediated through a specific soluble receptor, we have characterized this protein. The PROb cells contained more specific glucocorticoid-binding sites (approximately 170,000 sites per cell) than the regressive ones (REGb cells; approximately 100,000 sites per cell). In both clones, the receptor was associated with the Mr approximately 90,000 heat shock protein to yield large complexes (Stokes radius Rs approximately 7.5 nm), which were dissociated to the same extent upon heat- and salt-treatment. The steroid- and DNA-binding unit of the receptor, characterized under denaturing conditions using an anti-receptor monoclonal antibody, was found to be more degraded in the PROb cell line.
Denis
M G
MG
Department of Medical Biochemistry, INSERM CJF 90-11, U.F.R. of Medicine, Nantes, France.
Chadéneau
C
C
Blanchardie
P
P
Lustenberger
P
P
D000230:Adenocarcinoma; D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D003110:Colonic Neoplasms; D003907:Dexamethasone / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D005938:Glucocorticoids / Q000494:pharmacology*; D007700:Kinetics; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000302:isolation & purification / Q000378:metabolism; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D005938:Glucocorticoids; D009363:Neoplasm Proteins; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone