Role of the c-myc proto-oncogene in the proliferation of hereditary gingival fibromatosis fibroblasts

David Tipton, Ernest S. Woodard, Mark A. Baber, Mustafa Kh Dabbous

Research output: Contribution to journalArticle

11 Citations (Scopus)

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)-β 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 ≤0.02). All cells expressed c-myc mRNA at quiescence and ≥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 μM c-myc antisense ODN (14% decrease; P ≤0.006) and 8 μM c-myc antisense ODN (∼80% decrease; P≤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). Conclusion: Data suggest that elevated proliferation of an HGF fibroblast cell line is related to elevated c-myc expression.

Original languageEnglish (US)
Pages (from-to)360-369
Number of pages10
JournalJournal of periodontology
Volume75
Issue number3
DOIs
StatePublished - Mar 1 2004

Fingerprint

myc Genes
Fibroblasts
Serum
Fibronectins
Collagen
Cell Line
Fibromatosis, Gingival, Type 1
Antisense Oligonucleotides
Transforming Growth Factors
Bromodeoxyuridine
Electrophoresis
Enzyme-Linked Immunosorbent Assay
Polymerase Chain Reaction
Messenger RNA
DNA
Growth

All Science Journal Classification (ASJC) codes

  • Periodontics

Cite this

Role of the c-myc proto-oncogene in the proliferation of hereditary gingival fibromatosis fibroblasts. / Tipton, David; Woodard, Ernest S.; Baber, Mark A.; Dabbous, Mustafa Kh.

In: Journal of periodontology, Vol. 75, No. 3, 01.03.2004, p. 360-369.

Research output: Contribution to journalArticle

Tipton, David ; Woodard, Ernest S. ; Baber, Mark A. ; Dabbous, Mustafa Kh. / Role of the c-myc proto-oncogene in the proliferation of hereditary gingival fibromatosis fibroblasts. In: Journal of periodontology. 2004 ; Vol. 75, No. 3. pp. 360-369.
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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)-β 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 ≤0.02). All cells expressed c-myc mRNA at quiescence and ≥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 μM c-myc antisense ODN (14{\%} decrease; P ≤0.006) and 8 μM c-myc antisense ODN (∼80{\%} decrease; P≤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). Conclusion: Data suggest that elevated proliferation of an HGF fibroblast cell line is related to elevated c-myc expression.",
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