NDLI: Promoter regions involved in density-dependent regulation of basic fibroblast growth factor gene expression in human astrocytic cells.

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Promoter regions involved in density-dependent regulation of basic fibroblast growth factor gene expression in human astrocytic cells.

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Promoter regions involved in density-dependent regulation of basic fibroblast growth factor gene expression in human astrocytic cells.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Florkiewicz, R. Kratz, E. Moffett, J. Stachowiak, M. K.
Description	Author Affiliation: Moffett J ( Barrow Neurological Institute, Laboratory of Molecular Neurobiology, Phoenix, Arizona 85013, USA.);
Abstract	Expression of mitogenic basic fibroblast growth factor (bFGF) in the central nervous system is inhibited by direct cell contact and is implicated in reactive and neoplastic transformation of astrocytes. The molecular mechanisms controlling expression of bFGF were examined in cultures of human astrocytes. Cell-density-dependent depletion of bFGF mRNA levels parallels changes in bFGF gene protein. Regulation of transcription of a bFGF luciferase reporter gene containing an upstream region (bp -1800 to +314) of the bFGF gene promoter mimicks the density-dependent regulation of the endogenous bFGF gene in transfected astrocytes. Deletion analysis has identified a fragment (bp -650 to -513) and sequences further downstream (bp -274 to +314) as the regions required for the regulation of bFGF gene activity by cell density. Unlike in astrocytes, changing the cell density of glioma cell cultures does not affect the levels of bFGF protein and mRNA. bFGF luciferase constructs were expressed at the same level in high- or low-density cultures of glioma cells, indicating altered regulation of the bFGF gene promoter. Electrophoretic mobility shift assays showed binding of nuclear proteins to a fragment of bFGF gene promoter from bp -650 to -453. This binding was abolished by a deletion of the upstream cell-density-responsive region (bp -650 to -512). Binding was observed with nuclear extracts from subconfluent astrocytes but was reduced in extracts from confluent astrocytes. Our results indicate that induction of bFGF in astrocytes upon reduction of cell density is mediated transcriptionally by positive trans-acting factors interacting with bFGF promoter. In contrast, nuclear proteins from glioma cells bind to the promoter region from bp -650 to -453 independent of cell density. Thus, the constitutive binding of trans-acting factor(s) to the region of the bFGF promoter from bp -650 to -453 may be responsible for the continuous expression of bFGF that leads to the uncontrolled growth of glioma cells.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	6
Volume Number	93
Language	English
Publisher	National Academy of Sciences
Publisher Date	1996-07-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Astrocytes Physiology Cell Count Fibroblast Growth Factor 2 Genetics Promoter Regions, Genetic Cells, Cultured DNA-Binding Proteins Metabolism Gene Expression Regulation, Neoplastic Glioma Pathology Histones Nuclear Proteins RNA, Messenger Transcriptional Activation Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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