Glucocorticoids and melanoma: receptor properties of dexamethasone sensitive and resistant tumors.
We have grown solid tumors using dexamethasone-sensitive (clone 6) and -resistant (clone 5) cells cloned from RPMI 3460 Syrian hamster melanoma. Clone 6 but not clone 5 tumor growth was retarded by dexamethasone, indicating that these tumors retain the growth sensitivity to the hormone characteristic of the cells from which they are derived. Both tumor types contain cytosolic glucocorticoid receptors (significantly higher levels in clone 5 tumors) with similar affinity and steroid specificity characteristics and these can exist as stable, activated (nuclear binding) complexes. Despite these similarities the receptor in the two tumor types differ by some physiochemical criteria. By sucrose gradient analysis, cytosols from both tumors contain 7S receptor complexes but clone 6 contains an additional 13S form. Activated receptors isolated by DEAE-cellulose chromatography from both clone 5 and 6 tumor cytosols sediment as a single peak at 4-5S. However, the DEAE-cellulose profiles indicate that clone 6 but not clone 5 activated complexes (Peak I) appear heterogeneous with respect to charge. Interestingly, DNA-cellulose chromatography indicates that activated receptors from clone 5 tumor cytosols may bind more tightly to DNA than those from clone 6. We are investigating these receptor differences in more detail to determine more precisely the role and pathways of action of glucocorticoid hormones in melanoma.
D000818:Animals; D002460:Cell Line; D002499:Centrifugation, Density Gradient; D002848:Chromatography, DEAE-Cellulose; D006224:Cricetinae; D003600:Cytosol / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D008545:Melanoma / Q000378:metabolism*; D008647:Mesocricetus; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D011987:Receptors, Steroid / Q000378:metabolism*
D011965:Receptors, Glucocorticoid; D011987:Receptors, Steroid; D003907:Dexamethasone