This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by MacLeod, C. L. Articles by Bourgeois, S. Search for Related Content PubMed PubMed Citation Articles by MacLeod, C. L. Articles by Bourgeois, S.

A New Murine Model System for the in Vitro Development of Thymoma Cell Heterogeneity

Regulatory Biology Laboratory [C. L. M., S. B.] and Cancer Biology Laboratory [R. H.], The Salk Institute, San Diego 92138, and Laboratory of Biomedical and Environmental Sciences, UCLA, Los Angeles 90024 [E. F. H.], California

We have established and characterized a continuous T-cell line derived from the bone marrow of an AKR mouse with disseminated lymphoma. 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, Pgp1, and H-2K^k 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. Furthermore, 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 glucocorticoid 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. These 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.

¹ Supported by Grant CA06932 from NIH and by the National Leukemia Association. To whom requests for reprints should be addressed, at University of California at San Diego, Cancer Center (T-011), La Jolla, CA 92023. Leukemia Society of America Special Fellow.

² Supported by Grant CA12386 from NIH and Grant DE-AM03-76-SF00012 from the Department of Energy.

³ Supported by Grant CA13287 from NIH.

⁴ Supported by Grants GM20868 and CA36146 from NIH.

Received 9/23/83. Accepted 1/27/84.

This article has been cited by other articles:

				M. S. Carter, J. Doskow, P. Morris, S. Li, R. P. Nhim, S. Sandstedt, and M. F. Wilkinson A Regulatory Mechanism That Detects Premature Nonsense Codons in T-cell Receptor Transcripts in Vivo Is Reversed by Protein Synthesis Inhibitors in Vitro J. Biol. Chem., December 1, 1995; 270(48): 28995 - 29003. [Abstract] [Full Text] [PDF]