Abstract
Human lymphoblastic leukemia cells of line CEM-C7 are glucocroticoid-sensitive and contain glucocorticoid receptors of wild-type characteristics. EL4 mouse lymphoma cells are resistant to lysis by glucocorticoids due to mutant receptors that exhibit abnormal DNA binding. Hybrids between the two cell lines were prepared and analyzed with respect to glucocorticoid responsiveness and to receptor types by DNA-cellulose chromatrography. Sensitive hybrid cell clones contained the CEM-C7-specific receptor in addition to the EL4 type of receptor. Several sensitive hybrid cell clones were used for selection of resistant segregants by growth in the presence of high concentrations of glucocorticoid. These segregants had lost the wild-type CEM-C7 receptor, while the EL4-specific receptor was retained. To identify the human chromosome that was lost concordantly with the CEM-C7 receptor the chromosomes of hybrid cells were studied by alkaline Giemsa (G-11) staining and trypsin/Giemsa banding. All hybrids contained human chromosomes in addition to one to two sets of EL4 chromosomes. Human chromosome 5 was present in all hybrid cell clones that expressed the CEM-C7 receptor and it was absent from those that did not. This absolute correlation was not observed for any other human chromosome. We conclude that the human gene for the glucocorticoid receptor is located on chromosome 5.
Full text
PDF




Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Alhadeff B., Velivasakis M., Siniscalco M. Simultaneous identification of chromatid replication and of human chromosomes in metaphases of man-mouse somatic cell hybrids. (With 1 color plate). Cytogenet Cell Genet. 1977;19(4):236–239. doi: 10.1159/000130814. [DOI] [PubMed] [Google Scholar]
- Claesson-Welsh L., Barker P. E., Larhammar D., Rask L., Ruddle F. H., Peterson P. A. The gene encoding the human class II antigen-associated gamma chain is located on chromosome 5. Immunogenetics. 1984;20(1):89–93. doi: 10.1007/BF00373450. [DOI] [PubMed] [Google Scholar]
- Creagan R. P., Chen S., Ruddle F. H. Genetic analysis of the cell surface: association of human chromosome 5 with sensitivity to diphtheria toxin in mouse-human somatic cell hybrids. Proc Natl Acad Sci U S A. 1975 Jun;72(6):2237–2241. doi: 10.1073/pnas.72.6.2237. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dellweg H. G., Hotz A., Mugele K., Gehring U. Active domains in wild-type and mutant glucocorticoid receptors. EMBO J. 1982;1(3):285–289. doi: 10.1002/j.1460-2075.1982.tb01161.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- FOLEY G. E., LAZARUS H., FARBER S., UZMAN B. G., BOONE B. A., MCCARTHY R. E. CONTINUOUS CULTURE OF HUMAN LYMPHOBLASTS FROM PERIPHERAL BLOOD OF A CHILD WITH ACUTE LEUKEMIA. Cancer. 1965 Apr;18:522–529. doi: 10.1002/1097-0142(196504)18:4<522::aid-cncr2820180418>3.0.co;2-j. [DOI] [PubMed] [Google Scholar]
- Francke U., Gehring U. Chromosome assignment of a murine glucocorticoid receptor gene (Grl-1) using intraspecies somatic cell hybrids. Cell. 1980 Dec;22(3):657–664. doi: 10.1016/0092-8674(80)90541-3. [DOI] [PubMed] [Google Scholar]
- Francke U., Oliver N. Quantitative analysis of high-resolution trypsin-giemsa bands on human prometaphase chromosomes. Hum Genet. 1978 Dec 18;45(2):137–165. doi: 10.1007/BF00286957. [DOI] [PubMed] [Google Scholar]
- Gasson J. C., Bourgeois S. A new determinant of glucocorticoid sensitivity in lymphoid cell lines. J Cell Biol. 1983 Feb;96(2):409–415. doi: 10.1083/jcb.96.2.409. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gasson J. C., Ryden T., Bourgeois S. Role of de novo DNA methylation in the glucocorticoid resistance of a T-lymphoid cell line. Nature. 1983 Apr 14;302(5909):621–623. doi: 10.1038/302621a0. [DOI] [PubMed] [Google Scholar]
- Gehring U. Genetic analysis of glucocorticoid action in neoplastic lymphoid cells. Adv Enzyme Regul. 1978;17:343–361. doi: 10.1016/0065-2571(79)90021-9. [DOI] [PubMed] [Google Scholar]
- Gehring U., Hotz A. Photoaffinity labeling and partial proteolysis of wild-type and variant glucocorticoid receptors. Biochemistry. 1983 Aug 16;22(17):4013–4018. doi: 10.1021/bi00286a004. [DOI] [PubMed] [Google Scholar]
- Gehring U., Mohit B., Tomkins G. M. Glucocorticoid action on hybrid clones derived from cultured myeloma and lymphoma cell lines. Proc Natl Acad Sci U S A. 1972 Nov;69(11):3124–3127. doi: 10.1073/pnas.69.11.3124. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gehring U. Specific receptors control steroid sensitivity in lymphoma cell hybrids. Mol Cell Endocrinol. 1980 Dec;20(3):261–274. doi: 10.1016/0303-7207(80)90042-8. [DOI] [PubMed] [Google Scholar]
- George D. L., Francke U. Regional mapping of human genes for hexosaminidase B and diphtheria toxin sensitivity on chromosome 5 using mouse X human hybrid cells. Somatic Cell Genet. 1977 Nov;3(6):629–638. doi: 10.1007/BF01539070. [DOI] [PubMed] [Google Scholar]
- Grody W. W., Schrader W. T., O'Malley B. W. Activation, transformation, and subunit structure of steroid hormone receptors. Endocr Rev. 1982 Spring;3(2):141–163. doi: 10.1210/edrv-3-2-141. [DOI] [PubMed] [Google Scholar]
- Higgins S. J., Gehring U. Molecular mechanisms of steroid hormone action. Adv Cancer Res. 1978;28:313–397. doi: 10.1016/s0065-230x(08)60650-8. [DOI] [PubMed] [Google Scholar]
- Jensen E. V., Greene G. L., Closs L. E., DeSombre E. R., Nadji M. Receptors reconsidered: a 20-year perspective. Recent Prog Horm Res. 1982;38:1–40. doi: 10.1016/b978-0-12-571138-8.50006-8. [DOI] [PubMed] [Google Scholar]
- Norman M. R., Thompson E. B. Characterization of a glucocorticoid-sensitive human lymphoid cell line. Cancer Res. 1977 Oct;37(10):3785–3791. [PubMed] [Google Scholar]
- Pfahl M., Bourgeois S. Analysis of steroid resistance in lymphoid cell hybrids. Somatic Cell Genet. 1980 Jan;6(1):63–74. doi: 10.1007/BF01538696. [DOI] [PubMed] [Google Scholar]
- Pfahl M., Kelleher R. J., Jr, Bourgeois S. General features of steroid resistance on lymphoid cell lines. Mol Cell Endocrinol. 1978 Apr;10(2):193–207. doi: 10.1016/0303-7207(78)90125-9. [DOI] [PubMed] [Google Scholar]
- Rousseau G. G. Structure and regulation of the glucocorticoid hormone receptor. Mol Cell Endocrinol. 1984 Nov;38(1):1–11. doi: 10.1016/0303-7207(84)90139-4. [DOI] [PubMed] [Google Scholar]
- Sheppard J. R., Wehner J. M., McSwigan J. D., Shows T. B. Chromosomal assignment of the gene for the human beta 2-adrenergic receptor. Proc Natl Acad Sci U S A. 1983 Jan;80(1):233–236. doi: 10.1073/pnas.80.1.233. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sibley C. H., Tomkins G. M. Isolation of lymphoma cell variants resistant to killing by glucocorticoids. Cell. 1974 Aug;2(4):213–220. doi: 10.1016/0092-8674(74)90013-0. [DOI] [PubMed] [Google Scholar]
- Venetianer A., Bajnoczky K., Gal A., Thompson E. B. Isolation and characterization of L-cell variants with altered sensitivity to glucocorticoids. Somatic Cell Genet. 1978 Sep;4(5):513–530. doi: 10.1007/BF01542923. [DOI] [PubMed] [Google Scholar]
- Yamamoto K. R., Gehring U., Stampfer M. R., Sibley C. H. Genetic approaches to steroid hormone action. Recent Prog Horm Res. 1976;32:3–32. doi: 10.1016/b978-0-12-571132-6.50008-7. [DOI] [PubMed] [Google Scholar]
- Yamamoto K., Floyd-Smith G., Francke U., Koch N., Lauer W., Dobberstein B., Schäfer R., Hämmerling G. J. The gene encoding the Ia-associated invariant chain is located on chromosome 18 in the mouse. Immunogenetics. 1985;21(1):83–90. doi: 10.1007/BF00372244. [DOI] [PubMed] [Google Scholar]
- Zawydiwski R., Harmon J. M., Thompson E. B. Glucocorticoid-resistant human acute lymphoblastic leukemic cell line with functional receptor. Cancer Res. 1983 Aug;43(8):3865–3873. [PubMed] [Google Scholar]



