NDLI: Transforming growth factor beta 1 suppression of c-myc gene transcription: role in inhibition of keratinocyte proliferation.

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Transforming growth factor beta 1 suppression of c-myc gene transcription: role in inhibition of keratinocyte proliferation.

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Transforming growth factor beta 1 suppression of c-myc gene transcription: role in inhibition of keratinocyte proliferation.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Pietenpol, J. A. Stein, R. W. Holt, J. T. Moses, H. L.
Description	Author Affiliation: Pietenpol JA ( Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, TN 37232.);
Abstract	Transforming growth factor beta 1 (TGF-beta 1) is a potent growth inhibitor for many cell types, including most epithelial cells. However, the mechanism of growth inhibition is unknown. In skin keratinocytes, TGF-beta 1 has been shown to inhibit growth and to rapidly reduce c-myc expression. It has been demonstrated that protein synthesis is required for TGF-beta 1 regulation of c-myc in keratinocytes. Here we present evidence that treatment of mouse BALB/MK keratinocyte cells with either antisense c-myc oligonucleotides or TGF-beta 1 inhibited cell entry into S phase. These results suggest that TGF-beta inhibition of c-myc expression may be essential for growth inhibition by TGF-beta 1. The block in c-myc expression by TGF-beta 1 occurred at the level of transcriptional initiation. Studies with a series of 5' deletion c-myc/chloramphenicol acetyltransferase constructs indicated that a cis regulatory element(s), which resides between positions -100 and +71 relative to P1 transcription start site, is responsible for the TGF-beta 1 responsiveness. Based on these data, it is proposed that the mechanism of TGF-beta 1 growth inhibition involves synthesis or modification of a protein that may interact with a specific element(s) in the 5' regulatory region of the c-myc gene, resulting in inhibition of transcriptional initiation.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	10
Volume Number	87
Language	English
Publisher	National Academy of Sciences
Publisher Date	1990-06-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Keratinocytes Cytology Proto-Oncogene Proteins Genetics Proto-Oncogenes Drug Effects Suppression, Genetic Transcription, Genetic Transforming Growth Factors Pharmacology Animals Cell Division Cell Nucleus Metabolism Cells, Cultured Chloramphenicol O-Acetyltransferase DNA Replication Gene Expression Enzymology Mice Mice, Inbred BALB C Molecular Sequence Data Oligodeoxyribonucleotides Protein-Tyrosine Kinases Proto-Oncogene Proteins C-myc Restriction Mapping Transfection Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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