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Nuclear Binding of Steroid-Receptor Complex to Lymphosarcoma P1798 Resistant and Sensitive Cells and Effect of Concanavalin A on Receptor Levels¹

Grace Cancer Drug Center, Roswell Park Memorial Institute, Buffalo, New York 14263

Glucocorticoid-resistant P1798 cell lines have been found to contain levels of glucocorticoid receptor comparable to receptor levels in glucocorticoid-sensitive P1798 cells. Previously, most of the P1798 resistant cells examined were found to contain 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 to 50% lower levels of nuclear binding than did 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 both temperature dependent (effective at 37° but not 0°) and time dependent. Thus glucocorticoid resistance of P1798 cells appears to have a more complex mechanism than previously proposed.

¹ These studies were supported in part by USPHS Grants CA-05016 and CA-05671 and by American Cancer Society Grant Cl-130.

² Recipient of National Cancer Institute Postdoctoral Fellowship Grant CA-01543. Present address: Medical College of Ohio at Toledo, Department of Medicine, Toledo, Ohio 43699.

Received 6/27/77. Accepted 8/30/77.