Regulation of Expression of Transforming Growth Factor-β2 by Transforming Growth Factor-β Isoforms is Dependent upon Cell Type

Abstract

The effect of three different isoforms of transforming growth factor-β (TGF-β) on the expression of TGF-β2 mRNA was studied in several continuous tumor cell lines. As previously reported for the mouse fibroblast cell line AKR-2B, the expression of TGF-β2 mRNA transcripts of 5.4, 4.7, 3.7 and 3.0 kb was decreased after a 24 hr treatment with 5ng/ml of TGF-β1, TGF-β2 or TGF-β3. In A549, HBL-100 and BSC-1 epithelial cell lines, five distinct TGF-β2 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-β1, TGF-β2 or TGF-β3 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-β proteins was dose (5 ng/ml) and time (3–6 hr) dependent. A similar 2–3 fold increase in the level of secreted TGF-β2 was observed following treatment of A549 cells with TGF-β1. Basal level and induced expression of TGF-β2 mRNA in response to TGF-β isoforms was decreased in the presence of actinomycin D. In all cell lines studied, the expression of the 2.5 kb TGF-β1 mRNA was relatively unchanged or markedly increased in response to treatment with TGF-β. These studies support the hypothesis that expression of TGF-β2 is regulated by members of the TGF-β family and is dependent upon cell type.

Key Words:

• gene expression
• transforming growth factor-β