title: Role of the c-myc proto-oncogene in the proliferation of hereditary gingival fibromatosis fibroblasts.
abstract: BACKGROUND
  Hereditary gingival fibromatosis (HGF) is a fibrotic gingival enlargement. In previous work, HGF fibroblasts grew faster and produced more collagen and fibronectin (FN) than normal gingival (GN) fibroblasts. HGF FN and collagen production, but not proliferation, were under autocrine transforming growth factor (TGF)-beta control, suggesting other means of activation of HGF proliferation. Elevated/prolonged expression of the proto-oncogene c-myc is implicated in disregulation of cell growth. The objectives of this study were to: 1) determine if c-myc expression is abnormal in quiescent and serum-stimulated HGF and GN fibroblasts and 2) determine the relationship between c-myc expression and fibroblast proliferation using a c-myc antisense oligonucleotide (ODN).
  
  
  METHODS
  Proliferation was determined by enzyme-linked immunosorbent assay (ELISA), measuring incorporation of bromodeoxyuridine into DNA. Expression of c-myc was determined by quantitative polymerase chain reaction (PCR), using incorporation of fluorescent dCTP and detection via electrophoresis.
  
  
  RESULTS
  Proliferation was minimal until 24 hours or more after serum stimulation, when HGF proliferation was greater than GN (P < or = 0.02). All cells expressed c-myc mRNA at quiescence and > or = 1 hour after serum stimulation. Expression of c-myc in quiescent HGF fibroblasts was elevated, and it peaked and remained higher after serum stimulation than in GN cells. Proliferation of an HGF cell line was inhibited by 4 microM c-myc antisense ODN (14% decrease; P < or = 0.006) and 8 microM c-myc antisense ODN (approximately 80% decrease; P < or = 0.0001), but generally not by c-myc sense ODN. This effect was reversed by hybridizing the c-myc antisense and sense ODNs (P = 0.007).
  
  
  CONCLUSIONS
  Data suggest that elevated proliferation of an HGF fibroblast cell line is related to elevated c-myc expression.
authors.affiliation: Dental Research Center, Department of Periodontology, College of Dentistry, University of Tennessee Health Science Center, Memphis, TN 38163, USA. dtipton@utmem.edu
authors.forename: David A
authors.initials: DA
authors.lastname: Tipton
authors.forename: Ernest S
authors.initials: ES
authors.lastname: Woodard
authors.forename: Mark A
authors.initials: MA
authors.lastname: Baber
authors.forename: Mustafa Kh
authors.initials: MKh
authors.lastname: Dabbous
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D016022:Case-Control Studies; D002453:Cell Cycle / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D002460:Cell Line; D002648:Child; D003094:Collagen / Q000235:genetics; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D005351:Fibromatosis, Gingival / Q000235:genetics* / Q000473:pathology; D005353:Fibronectins / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics; D016259:Genes, myc / Q000235:genetics*; D005881:Gingiva / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D016376:Oligonucleotides, Antisense; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D005353:Fibronectins; C000715470:MAS1 protein, human; D016376:Oligonucleotides, Antisense; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D003094:Collagen