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.
Normanno
N
N
Oncologia Sperimentale D, ITN-Fondazione Pascale, 80131 Napoli, Italy. nicnorm@yahoo.com
Bianco
C
C
De Luca
A
A
Salomon
D S
DS
D066258:Amphiregulin; D000818:Animals; D066259:Betacellulin; D066255:EGF Family of Proteins; D004815:Epidermal Growth Factor / Q000502:physiology*; D066260:Epiregulin; D058851:GPI-Linked Proteins; D006023:Glycoproteins / Q000502:physiology; D006133:Growth Substances / Q000502:physiology; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000502:physiology; D009363:Neoplasm Proteins / Q000502:physiology; D009369:Neoplasms / Q000473:pathology*; D020880:Neuregulins / Q000502:physiology; D016211:Transforming Growth Factor alpha / Q000502:physiology
C587848:AREG protein, human; D066258:Amphiregulin; C587849:Areg protein, mouse; C587851:BTC protein, human; D066259:Betacellulin; C587852:Btc protein, mouse; D066255:EGF Family of Proteins; C587880:EREG protein, human; D066260:Epiregulin; C587881:Ereg protein, mouse; D058851:GPI-Linked Proteins; D006023:Glycoproteins; D006133:Growth Substances; C587883:HBEGF protein, human; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D020880:Neuregulins; C070636:TDGF1 protein, human; C423567:TMEFF2 protein, human; C489450:Tdgf1 protein, mouse; C486585:Tmeff1 protein, mouse; D016211:Transforming Growth Factor alpha; D004815:Epidermal Growth Factor