EGF receptor and its ligands, EGF and TGF-alpha, in developing and neoplastic human odontogenic tissues

Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) regulate cell proliferation and functional maturation through the EGF receptor (EGF-R). Their roles in human tooth development and odontogenic tumorigenesis have not been explored. We studied the expression of EGF, TGF-alpha and EGF-R in human fetal teeth (cap stage to early hard tissue formation) and various odontogenic tumors. EGF-R mRNA and immunoreactive cells were mostly located in odontogenic epithelium. EGF-R expression was subject to temporospatial variation at different stages of tooth development. EGF and TGF-alpha mRNAs were detected in fetal teeth only by the reverse transcription polymerase chain reaction (RT-PCR). However, EGF and TGF-alpha immunoreactive cells were demonstrated in epithelial elements of tooth germ, suggesting that the peptides partially originate from non-odontogenic sources. In odontogenic tumors, EGF-R mRNA and immunoreactivity were confined to neoplastic epithelium. Transcripts for TGF-alpha but not for EGF were detected in tumors of odontogenic epithelial, epithelial-ectomesenchymal and ectomesenchymal origins. It is concluded that regulation of EGF-R expression is developmentally regulated in human odontogenesis. Furthermore, the odontogenic epithelium is the main target tissue for both EGF and TGF-alpha during tooth development. TGF-alpha and its receptor may also be involved in odontogenic tumorigenesis.