Transforming growth factor beta 1 positively regulates its own expression in normal and transformed cells.
Transforming growth factor beta 1 (TGF-beta 1) regulates the growth, differentiation, or function of nearly all cell types. We now report that TGF-beta 1 increases steady-state levels of its own message in six different normal and transformed cells in culture. Accumulation of TGF-beta 1 mRNA can be detected by Northern blot analysis within 3 h of addition of the peptide to cells, and enhanced message levels persist as long as TGF-beta 1 is present in the culture medium. This autoinduction is half-maximal at approximately 10 PM TGF-beta 1, and maximal stimulation corresponds to a 2-3-fold increase in transcript levels. In normal rat kidney cells, the rise in TGF-beta 1 mRNA is actinomycin D-sensitive and is accompanied by a parallel (approximately 3-fold) increase in secretion of TGF-beta 1 protein in the culture medium of treated cells, as detected by immunoprecipitation of biosynthetically labeled 35S-labeled TGF-beta 1 using specific anti-TGF-beta 1 antibodies. Treatment of normal rat kidney cells with either epidermal growth factor or platelet-derived growth factor also results in an increase in TGF-beta 1 mRNA (2-3-fold), although epidermal growth factor and TGF-beta 1 appear to act via distinct mechanisms since their combined effects are greater than additive.
Van Obberghen-Schilling
E
E
Laboratory of Chemoprevention, National Cancer Institute, Bethesda, Maryland 20892.
Roche
N S
NS
Flanders
K C
KC
Sporn
M B
MB
Roberts
A B
AB
D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D003094:Collagen / Q000235:genetics; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics; D006706:Homeostasis; D006801:Humans; D010455:Peptides / Q000235:genetics / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D015291:Transforming Growth Factors
D010455:Peptides; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D003609:Dactinomycin; D004815:Epidermal Growth Factor; D015291:Transforming Growth Factors; D003094:Collagen; D003513:Cycloheximide; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases