TGFA

Transforming growth factors (TGFs) are potent mitogeni c polypeptides. Two classes of TGFs have been identified: TGFα and TGFβ . TGF α is synthesized as a 160 amino acid, trans membrane precursor. The precursor undergoes sequential external proteolytic cleavage, releasing TGFα species ranging in molecular weight from 6-25 kDa. Mature TGFα is an acid- and heat-stable 50 amino acid polypeptide of 5.5 kDa. It is secreted by a variety of transformed cells and tumors, and by a number of embryoni c cells as well as some normal adult tissues including the brain and skin keratinocytes. Mature TGF α is approximately 30% homologous, at the amino acid level, to epidermal growth factor (EGF). TGF α binds to the EGF receptor, mediates tyrosine phosphorylation of the receptor, and promotes anchorage-independent growth of normal rat fibroblasts in soft agar in the presence of transforming growth factor-beta. Transformation of cells, in vitro, by certain viruses including SV40 and polyoma virus, as well as transformation by the activated ras oncogene can lead to increased secretion of TGF α. TGF α may play a role in tumor formation by an autocrine/paracrine mechanism whereby TGFα promotes and sustains the transformed character of the cells from which it is secreted as well as that of neighboring cells. The biological relevance of TGF α in tumor development is supported by reports that multiple molecular weight forms of TGF α may be found in the urine of cancer patients in amounts which differ from those found in normal urine samples. TGF α may also play a role in normal development including wound healing. The major difficulty impeding the investigation of the normal and pathological roles of TGFα in vivo has been the use of activity-based biological assays that do not distinguish between TGFα and other related molecules (e.g., EGF). The TGF α ELISA is highly specific and can detect less than 10 pg/ml of human TGF α in a variety of biological fluids and tissue culture media.

TFGA; TGF-alpha; protransforming growth factor alpha;