Role of TGF-beta in normal differentiation and oncogenesis in rat liver.

Transforming growth factor-beta 1 (TGF-beta 1) is capable of eliciting a myriad of biological responses associated with cellular proliferation, as well as effects unrelated to the control of cell growth. We examined the possible role of TGF-beta 1 in the differentiation of rat liver epithelial (RLE) cells in vitro and studied the cellular distribution of TGF-beta 1 transcripts and protein during in vivo differentiation of oval cells. Furthermore, we followed the cellular distribution of TGF-beta 1 transcripts and protein during chemical hepatocarcinogenesis. By using in situ hybridization and immunohistochemical techniques, we showed that both TGF-beta 1 transcripts and protein are localized in nonparenchymal cells in normal liver, are expressed in oval cells during very early stages of hepatocytic differentiation in vivo, and are exclusively expressed in the nontumorous mesenchymal cell compartment during hepatocarcinogenesis. Furthermore, we showed that TGF-beta 1 is capable of inducing differentiation of RLE cells in vitro consistent with early stages of hepatocytic lineage differentiation. Our data indicate that the RLE cells similar to the oval cells in vivo may be an epithelial progenitor cell for hepatocytic cell lineage in adult mammalian liver.