title: EGF receptor and its ligands, EGF and TGF-alpha, in developing and neoplastic human odontogenic tissues.
abstract: 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.
authors.affiliation: Department of Oral Pathology, University of Turku, Finland.
authors.forename: K
authors.initials: K
authors.lastname: Heikinheimo
authors.forename: R
authors.initials: R
authors.lastname: Voutilainen
authors.forename: R P
authors.initials: RP
authors.lastname: Happonen
authors.forename: P J
authors.initials: PJ
authors.lastname: Miettinen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001483:Base Sequence; D002675:Child, Preschool; D046508:Culture Techniques; D004815:Epidermal Growth Factor / Q000032:analysis / Q000096:biosynthesis / Q000502:physiology*; D066246:ErbB Receptors / Q000032:analysis / Q000096:biosynthesis / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009808:Odontogenic Tumors / Q000737:chemistry / Q000503:physiopathology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D014070:Tooth / Q000196:embryology*; D016211:Transforming Growth Factor alpha / Q000032:analysis / Q000096:biosynthesis / Q000502:physiology*
chemical_list: D012333:RNA, Messenger; D016211:Transforming Growth Factor alpha; D004815:Epidermal Growth Factor; D066246:ErbB Receptors