NUCLEAR BINDING OF STEROID-RECEPTOR COMPLEX TO LYMPHOSARCOMA P1798 RESISTANT AND SENSITIVE CELLS AND EFFECT OF CONCANAVALIN-A ON RECEPTOR LEVELS

Abstract

Glucocorticoid-resistant P1798 mouse cell lines contained levels of glucocorticoid receptor comparable to receptor levels in glucocorticoid-sensitive P1798 cells. Previously, most of the P1798 resistant cells examined contained low levels of glucocorticoid receptor, and this was thought to account for the resistance of these cells to glucocorticoid treatment. Resistant cells with high receptor levels exhibited 10-50% lower levels of nuclear binding than sensitive cells. In addition, 90% of the glucocorticoid-receptor complex could be extracted from resistant nuclei with 0.2 M NaCl, while only 55% of the complex could be extracted from sensitive nuclei, indicating that the affinity of the hormone-receptor complex for resistant nuclei may be weaker than the affinity of the hormone-receptor complex for sensitive nuclei. The effect of concanavalin A was also examined in P1798 sensitive and resistant cells. Concanavalin A effectively lowered glucocorticoid receptor levels in the sensitive cells by 45%, while receptor levels of the resistant cells were only slightly lowered. The effect of concanavalin A was temperature (effective at 37.degree. but not 0.degree. C) and time dependent. Glucocorticoid resistance of P1798 cells appears to have a more complex mechanism than previously proposed.