Glucocorticoid effects and receptors in two rat colon carcinoma cell lines differing by their tumorigenicity.
Steroid hormones, regulators of cell differentiation and proliferation, are believed to play a role in carcinogenesis. Glucocorticoid hormones in particular modulate the expression of a number of proteins implicated in this process. 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 hormonal treatment, glucocorticoid hormones induced fibronectin secretion by the two clones, whereas PROb cells were found to secrete an additional Mr approximately 43,000 protein. The cellular effect of glucocorticoid hormones being mediated through a specific soluble receptor, we have characterized this protein. The progressive cells (PROb) 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 progressive cell line.
Berrada
A
A
Department of Medical Biochemistry, Nantes University Hospital, France.
Denis
M G
MG
Blanchardie
P
P
Chadeneau
C
C
Lustenberger
P
P
D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D003110:Colonic Neoplasms / Q000473:pathology; D003600:Cytosol / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D007700:Kinetics; D046911:Macromolecular Substances; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000302:isolation & purification; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D014158:Transcription, Genetic
D006360:Heat-Shock Proteins; D046911:Macromolecular Substances; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D011965:Receptors, Glucocorticoid