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Reduced signal transduction through glucocorticoid receptor in Burkitt's lymphoma cell lines.
Virology. 1994 Mar; 199(2):339-53.V

Abstract

Signal transduction through the glucocorticoid receptor (GR) was shown to be significantly reduced in Epstein-Barr virus (EBV)-positive group I Burkitt's lymphoma (BL) cell lines compared to human B-lymphocytes immortalized by EBV (LCLs). On the basis of hormone binding assays, nuclear DNA binding activity, and transactivation assays the response was reduced 5- to 10-fold. Direct sequence analysis of the expressed glucocorticoid receptor mRNA in two BL cell lines indicated that the phenotype did not result from mutation of the GR gene. By preparing a high-titer polyclonal antiserum against the t-1 region of the human GR, we further showed that the deficient GR response in BLs is largely reflected in reduced GR steady-state protein levels in BL cells compared to LCLs. However, the level of GR mRNA varies less between the BL cell lines and the LCLs. The Cp promoter of EBV which normally drives expression of the EBNA gene family in EBV-immortalized LCLs contains a functional glucocorticoid response element. Transfection of GR expression constructs to group I BL cells converted the GR response to approximately LCL levels both with respect to hormone binding and glucocorticoid-dependent transcription of a glucocorticoid-dependent promoter. A modest activation of EBNA-2 expression was seen in some such cell lines, suggesting that the lower GR response contributes to the down-regulation of EBNA expression observed in BL.

Authors+Show Affiliations

Ludwig Institute for Cancer Research, St. Mary's Hospital Medical School, London, United Kingdom.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

8122366

Citation

Sinclair, A J., et al. "Reduced Signal Transduction Through Glucocorticoid Receptor in Burkitt's Lymphoma Cell Lines." Virology, vol. 199, no. 2, 1994, pp. 339-53.
Sinclair AJ, Jacquemin MG, Brooks L, et al. Reduced signal transduction through glucocorticoid receptor in Burkitt's lymphoma cell lines. Virology. 1994;199(2):339-53.
Sinclair, A. J., Jacquemin, M. G., Brooks, L., Shanahan, F., Brimmell, M., Rowe, M., & Farrell, P. J. (1994). Reduced signal transduction through glucocorticoid receptor in Burkitt's lymphoma cell lines. Virology, 199(2), 339-53.
Sinclair AJ, et al. Reduced Signal Transduction Through Glucocorticoid Receptor in Burkitt's Lymphoma Cell Lines. Virology. 1994;199(2):339-53. PubMed PMID: 8122366.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reduced signal transduction through glucocorticoid receptor in Burkitt's lymphoma cell lines. AU - Sinclair,A J, AU - Jacquemin,M G, AU - Brooks,L, AU - Shanahan,F, AU - Brimmell,M, AU - Rowe,M, AU - Farrell,P J, PY - 1994/3/1/pubmed PY - 1994/3/1/medline PY - 1994/3/1/entrez SP - 339 EP - 53 JF - Virology JO - Virology VL - 199 IS - 2 N2 - Signal transduction through the glucocorticoid receptor (GR) was shown to be significantly reduced in Epstein-Barr virus (EBV)-positive group I Burkitt's lymphoma (BL) cell lines compared to human B-lymphocytes immortalized by EBV (LCLs). On the basis of hormone binding assays, nuclear DNA binding activity, and transactivation assays the response was reduced 5- to 10-fold. Direct sequence analysis of the expressed glucocorticoid receptor mRNA in two BL cell lines indicated that the phenotype did not result from mutation of the GR gene. By preparing a high-titer polyclonal antiserum against the t-1 region of the human GR, we further showed that the deficient GR response in BLs is largely reflected in reduced GR steady-state protein levels in BL cells compared to LCLs. However, the level of GR mRNA varies less between the BL cell lines and the LCLs. The Cp promoter of EBV which normally drives expression of the EBNA gene family in EBV-immortalized LCLs contains a functional glucocorticoid response element. Transfection of GR expression constructs to group I BL cells converted the GR response to approximately LCL levels both with respect to hormone binding and glucocorticoid-dependent transcription of a glucocorticoid-dependent promoter. A modest activation of EBNA-2 expression was seen in some such cell lines, suggesting that the lower GR response contributes to the down-regulation of EBNA expression observed in BL. SN - 0042-6822 UR - https://www.unboundmedicine.com/medline/citation/8122366/Reduced_signal_transduction_through_glucocorticoid_receptor_in_Burkitt's_lymphoma_cell_lines_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0042-6822(84)71132-9 DB - PRIME DP - Unbound Medicine ER -