A NEW MURINE MODEL SYSTEM FOR THE IN VITRO DEVELOPMENT OF THYMOMA CELL HETEROGENEITY

  • 1 January 1984
    • journal article
    • research article
    • Vol. 44  (5) , 1784-1790
Abstract
A continuous T cell line [SL12], derived from the bone marrow of an AKR mouse with disseminated lymphoma was established and characterized. The original tumor cell line is heterogeneous with respect to several markers of thymocyte differentiation. Clones from the line differ in the expression of ThB, Pgp-1 and H-2Kk surface antigens. These clones also differ in their sensitivity to glucocorticoid-induced cell lysis. The quantity, affinity and nuclear translocation properties of the glucocorticoid receptor are similar in the hormone-sensitive and -resistant clones. Dexamethasone-resistant T cells can be selected in vitro from freshly cloned cells sensitive to hormone-induced lysis at high frequency and without mutagenesis. Of several randomly sampled, spontaneously arising, independently derived dexamethasone resistant clones, all show a coordinate reduction in cell surface Thy-1 and ThB expression with no detectable changes in glucocortocoid receptor properties. Following treatment with the DNA-demethylating agent 5-azacytidine, the original dexamethasone-resistant T cell line as well as the dexamethasone-resistant derivatives obtained in vitro regain sensitivity to lysis. The results collectively suggest a role of DNA methylation in hormone resistance and are consistent with a model of thymocyte differentiation in which a glucocorticoid-sensitive cell is the progenitor of hormone-resistant T cells.