| c-Myc and cyclin D3 (CcnD3) genes are independent targets for glucocorticoid inhibition of lymphoid cell proliferation. | |
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MedLine Citation:
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PMID: 7664296 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Glucocorticoids inhibit the expression of critical cell cycle-regulatory genes. The G1 cyclin gene CcnD3, which encodes cyclin D3, is inhibited by dexamethasone in P1798 murine T lymphoma cells. Glucocorticoids also inhibit expression of the catalytic partner of cyclin D3, Cdk4. Inhibition of these two genes results in a decrease in the ability to phosphorylate the Rb-1 tumor suppressor gene product. Stable transformation with SV40 T antigen expression vectors prevents glucocorticoid-mediated cell cycle arrest, which is consistent with the conclusion that glucocorticoids inhibit Rb-1 phosphorylation. Overexpression of cyclin D3 suffices to restore Rb-kinase activity in glucocorticoid-treated cells. Nevertheless, overexpression of cyclin D3 does not prevent glucocorticoid inhibition of cell proliferation. Cells transformed with Cdk4 expression vectors, with or without cyclin D3 expression vectors, also undergo G0 arrest in the presence of dexamethasone. Glucocorticoids inhibit c-Myc expression in lymphoid cells, and transient expression of c-Myc protein attenuates the lytic response in glucocorticoid-treated human leukemia cells (R. Thulasi, D. V. Harbour, and E. B. Thompson, J. Biol. Chem., 268: 18306-16312, 1993). However, P1798 cells stably transfected with c-Myc expression vectors are sensitive to glucocorticoid-mediated G0 arrest. Such transformants withdraw from the cell cycle when treated with dexamethasone. P1798 cells were transformed so as to express both c-Myc protein and cyclin D3 in the presence of glucocorticoids. These Myc/D3 cells continue to proliferate in the presence of dexamethasone, and virtually all of these cells are capable of entering S phase in the presence of the steroid. Rapid apoptotic cell death occurs when wild-type P1798 cells are treated with dexamethasone in serum-free medium. Myc-transformed and cyclin D3-transformed cells also die rapidly when treated with glucocorticoids in the absence of serum. T antigen transformants are resistant to glucocorticoid-mediated apoptosis in serum-free medium. Double transformants that express both cyclin D3 and c-Myc are also resistant to apoptosis in the presence of dexamethasone. We conclude that inhibition of both CcnD3 and c-Myc genes is critical to glucocorticoid-mediated G0 arrest. Furthermore, those genes that convey resistance to growth arrest also convey resistance to cell death. |
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Authors:
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K Rhee; W Bresnahan; A Hirai; M Hirai; E A Thompson |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Cancer research Volume: 55 ISSN: 0008-5472 ISO Abbreviation: Cancer Res. Publication Date: 1995 Sep |
Date Detail:
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Created Date: 1995-10-06 Completed Date: 1995-10-06 Revised Date: 2012-06-25 |
Medline Journal Info:
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Nlm Unique ID: 2984705R Medline TA: Cancer Res Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 4188-95 Citation Subset: IM |
Affiliation:
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Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston 77550-0645, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antigens, Polyomavirus Transforming / physiology Cell Death / drug effects Cell Division / drug effects Cyclin D3 Cyclin-Dependent Kinase 4 Cyclin-Dependent Kinases* Cyclins / genetics* Drug Resistance G0 Phase Genes, myc / drug effects* Glucocorticoids / pharmacology* Mice Phosphorylation Protein-Serine-Threonine Kinases / genetics Proto-Oncogene Proteins* Retinoblastoma Protein / metabolism Simian virus 40 / immunology Tumor Cells, Cultured |
| Grant Support | |
ID/Acronym/Agency:
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R37-CA24347/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antigens, Polyomavirus Transforming; 0/CCND3 protein, human; 0/Ccnd3 protein, mouse; 0/Cyclin D3; 0/Cyclins; 0/Glucocorticoids; 0/Proto-Oncogene Proteins; 0/Retinoblastoma Protein; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.22/Cdk4 protein, mouse; EC 2.7.11.22/Cyclin-Dependent Kinase 4; EC 2.7.11.22/Cyclin-Dependent Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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