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 Ip, M. M. Articles by Young, D. A. Search for Related Content PubMed PubMed Citation Articles by Ip, M. M. Articles by Young, D. A.

The Truncated Glucocorticoid Receptor in the P1798 Mouse Lymphosarcoma Is Associated with Resistance to Glucocorticoid Lysis but not to Other Glucocorticoid-induced Functions¹

Grace Cancer Drug Center, Roswell Park Cancer Institute, Buffalo, New York 14263 [M. M. I., W. K. S., D. S.], and Departments of Medicine, Biochemistry, and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642 [D. A. Y.]

Glucocorticoid receptors in lines of the P1798 mouse lymphosarcoma either sensitive or resistant to glucocorticoid-induced lysis have been characterized and their functional significance determined. The glucocorticoid receptor from the cortisol-sensitive tumor is an M_r 98,000 protein with a Stokes radius of 7.4 nm in the oligomeric, non-DNA-binding state and 5.6 nm in the transformed, DNA-binding state. This receptor binds glucocorticoid and reacts with the BUGR-2 monoclonal antibody. In contrast, two abnormal receptor species were identified in the cortisol-resistant tumor. One is an M_r 98,000 non-steroid-binding but immunologically reactive protein. The other is an M_r 45,000 species which contains both steroid- and DNA-binding sites but exhibits little or no reactivity with BUGR-2, suggesting that its NH₂ terminus is truncated in a region within or adjacent to the BURG epitope. This species had Stokes radii of 5.8 and 3.5 nm in nontransformed and transformed states, respectively. In both tumor lines, glucocorticoids stimulated the activities of glutamine synthetase and 5'-nucleotidase and the synthesis of glucocortin. However, glucocorticoid-induced tumor regression occurred only in the cortisol-sensitive tumor. Additionally, the glucocorticoid inducibility of a specific protein in the sensitive, but not in the resistant, tumor was demonstrated, as well as the presence of a protein specific to the resistant line. Taken together, these results suggest that the truncated glucocorticoid receptor in the P1798 lymphosarcoma is functional, although possibly in a more restricted gene-specific manner, and that the lysis defect, while possibly resulting from a truncated receptor, may also result from the inability of glucocorticoids to induce a critical protein in the pathway of programmed cell death and/or from the presence of a protein which inhibits the lytic response.

¹ This work was supported by grant BE-35 from the American Cancer Society (M. M. I.), NIH Core grant CA 16056 (M. M. I.), NIH grants DK 16177 and CA 47650 (D. A. Y.) and by grant 1774 from the Council for Tobacco Research (D. A. Y.).

² To whom reprint requests should be addressed, at Grace Cancer Drug Center, Roswell Park Cancer Institute, 666 Elm Street, Buffalo, NY 14263.

Received 12/17/90. Accepted 3/20/91.

This article has been cited by other articles:

				N. Z. LU and J. A. CIDLOWSKI The Origin and Functions of Multiple Human Glucocorticoid Receptor Isoforms Ann. N.Y. Acad. Sci., June 1, 2004; 1024(1): 102 - 123. [Abstract] [Full Text] [PDF]

				P. R. Mittelstadt and J. D. Ashwell Disruption of Glucocorticoid Receptor Exon 2 Yields a Ligand-Responsive C-Terminal Fragment that Regulates Gene Expression Mol. Endocrinol., August 1, 2003; 17(8): 1534 - 1542. [Abstract] [Full Text] [PDF]