| Abstract: | The mRNA expression and autoregulation of expression of the three isoforms of transforming growth factor-β (TGFβ) were examined in the mouse skin carcinogenesis model by northern analyses. We found that TGFβ3 mRNA levels followed a pattern similar to those of TGFβ1 during carcinogenesis: the levels were somewhat low in normal skin but became highly overexpressed in late-stage papillomas and squamous cell carcinomas (15- to 20-fold higher than in normal skin). On the other hand, the TGFβ2 mRNA levels remained relatively low in all benign and malignant tumors, even though the levels were higher than the nearly undetectable levels in normal skin. In a squamous cell carcinoma cell line (CH72), stable transfection and expression of a mutated simian TGFβ1 cDNA producing bioactive TGFβ1 significantly downregulated (mean greater than tenfold) TGFβ2 mRNA levels and modestly downregulated (about twofold) murine TGFβ1 expression but had no effect on TGFβ3 mRNA. In contrast, treatment of all CH72 clones with exogenous TGFβ1, TGFβ2, or TGFβ3 either had no effect or slightly downregulated TGFβ1 mRNA, upregulated TGFβ2 mRNA expression an average of twofold to threefold, and strongly upregulated (mean 13- to 27-fold) TGFβ3 mRNA levels. TGFβ treatment of primary cultures of mouse skin keratinocytes upregulated all three TGFβ mRNA levels slightly to moderately (1.3- to 5-fold). Thus, although TGFβ1 and TGFβ3 mRNA expressions were apparently coordinately upregulated during mouse skin carcinogenesis, the three TGFβ mRNAs were differentially regulated by stable transfection of active TGFβ1 versus exogenous TGFβ treatment in CH72 cells and by TGFβ treatments of normal keratinocytes versus carcinoma CH72 cells. Mol. Carcinog. 18:115–126, 1997. © 1977 Wiley-Liss, Inc. |
