Regulation of Fibroblastic and Epithelial Cell Function by Transforming Growth Factors

The transforming growth factors (TGF) were originally described as autocrine factors thought to be involved in neoplastic transformation, and were defined by their biologic effects on fibroblastic cells. These effects include stimulation of colony formation in soft agar and induction of morphologic transformation in monolayer culture. Although the early studies with TGF were somewhat misleading with regard to the currently known function of these factors, they did lead to the purification in cloning of two important growth regulatory peptides, TGFα and TGFβ. It is of considerable interest that one of these factors (TGFα) is a potent mitogen for a wide variety of cell types, while the other (TGFβ) is the most potent inhibitory peptide known for many cell types. In addition, both of these factors are produced by certain normal cells such as the skin keratinocyte which exhibit an opposing proliferative response to TGFα and TGFβ. This provides the mechanism for balanced autocrine control of proliferation by both positive and negative regulatory factors. The involvement of both positive and negative regulatory factors in the control of cell proliferation could provide for a more precise control of proliferation than could be achieved with a single regulatory pathway. This review will provide a brief background on TGFα and TGFβ (now known to repesent a large family of genes) and will concentrate on the production of and response to TGFα and TGFβ in a normal cell type, the skin keratinocyte. Changes that may occur with neoplastic transformation will also be addressed.