Regulation of expression of transforming growth factor-beta 2 by transforming growth factor-beta isoforms is dependent upon cell type.
The effect of three different isoforms of transforming growth factor-beta (TGF-beta) on the expression of TGF-beta 2 mRNA was studied in several continuous tumor cell lines. As previously reported for the mouse fibroblast cell line AKR-2B, the expression of TGF-beta 2 mRNA transcripts of 5.4, 4.7, 3.7 and 3.0 kb was decreased after a 24 hr treatment with 5 ng/ml of TGF-beta 1, TGF-beta 2 or TGF-beta 3. In A549, HBL-100 and BSC-1 epithelial cell lines, five distinct TGF-beta 2 mRNA transcripts of 5.8, 5.1, 4.0, 3.8 and 2.8 kb were detected by Northern blot analysis. Treatment of these cells with TGF-beta 1, TGF-beta 2 or TGF-beta 3 for 24 hr resulted in a 2-3 fold increase in the 5.8, 4.0 and 3.8 kb transcripts, with little detectable change in abundance of the 5.1 and 2.8 kb transcripts. The effect of the TGF-beta proteins was dose (5 ng/ml) and time (3-6 hr) dependent. A similar 2-3 fold increase in the level of secreted TGF-beta 2 was observed following treatment of A549 cells with TGF-beta 1. Basal level and induced expression of TGF-beta 2 mRNA in response to TGF-beta isoforms was decreased in the presence of actinomycin D. In all cell lines studied, the expression of the 2.5 kb TGF-beta 1 mRNA was relatively unchanged or markedly increased in response to treatment with TGF-beta.(ABSTRACT TRUNCATED AT 250 WORDS)
O'Reilly
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MA
Laboratory of Chemoprevention, National Cancer Institute, National Institutes of Health, Bethesda, MD 20814.
Danielpour
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D
Roberts
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AB
Sporn
M B
MB
D000818:Animals; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003609:Dactinomycin / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics; D013997:Time Factors; D014158:Transcription, Genetic / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000737:chemistry / Q000502:physiology*; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D003609:Dactinomycin