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 (TG F-alpha) regulate cell proliferation and functional maturation through the EGF receptor (EGF-R). Their roles in human tooth development and odontogenictumorigenesis have not been explored. We studied the expres sion of EGF, TGF-alpha and EGF-R in human fetal teeth (cap stage to ea rly 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 differen t stages of tooth development. EGF and TGF-alpha mRNAs were detected i n fetal teeth only by the reverse transcription polymerase chain react ion (RT-PCR). However, EGF and TGF-alpha immunoreactive cells were dem onstrated in epithelial elements of tooth germ, suggesting that the pe ptides partially originate from non-odontogenic sources. In odontogeni c 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 ecto mesenchymal origins. It is concluded that regulation of EGF-R expressi on is developmentally regulated in human odontogenesis. Furthermore, t he odontogenic epithelium is the main target tissue for both EGF and T GF-alpha during tooth development. TGF-alpha and its receptor may also be involved in odontogenic tumorigenesis.