The role of EGF-related peptides in tumor growth

The epidermal growth factor (EGF) family of peptides encodes several proteins that can function as growth factors. The EGF-like peptides, with the exception of proteins of the EGF-CFC subfamily, bind and activate tyrosine kinase receptors that belong to the erbB family. The EGF-like peptides are overexpressed in a majority of human carcinomas as compared with their nontransformed counterpart. By using different approaches, it has been shown that several different EGF-like peptides function as autocrine growth factors in carcinoma cell lines of different histological origin. Direct evidence that the EGF-like growth factors might function as transforming genes has been provided by in vitro and in vivo studies. In particular, the development of different transgenic mouse lines in which EGF-like growth factors have been overexpressed by means of tissue-specific or nonspecific promoters has provided invaluable information relating to their ability to function as dominantly transforming oncogenes. Cooperation of the EGF-like peptides with cellular protooncogenes in determining cell transformation has been demonstrated by using both in vitro and transgenic mice systems. Taken together, these data strongly suggest that the EGF-like peptides are involved in the pathogenesis of human carcinomas, and that they might represent suitable targets for novel therapeutic approaches.