TGF-β isoforms fail to modulate inositol phosphates and cAMP in normal and tumour-derived human oral keratinocytes

Adam J. Collier, Kathryn A. Elsegood, William Andrew Yeudall, Ian C. Paterson, Stephen S. Prime, Jonathan R. Sandy

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

This study examined inositol phosphate and cAMP regulation by TGF-β1, -β2 and -β3 in normal and tumour-derived human oral keratinocytes. Previous findings indicated that the cell lines expressed TGF-β1 cell surface receptors and had a range of response to exogenous TGF-β1, -β2 and -β3 from being refractory to the ligand to marked inhibition. Basal levels of inositol phosphates broadly reflected the differentiation status of the cells as demonstrated by involucrin expression, but did not correlate with responsiveness to TGF-β1, as measured previously by thymidine incorporation. Treatment of cells with bradykinin or serum caused up-regulation of inositol phosphate levels; by contrast, TGF-β1, -β2 and -β3 failed to modulate inositol phosphates. In two tumour-derived cell lines, the TGF-β isoforms had no effect on cAMP levels, despite a significant increase in cAMP using a potent agonist of adenylate cyclase (forskolin). Furthermore, the cAMP analogue, dibutyryl cAMP, failed to mimic the inhibitory or refractory responses of TGF-β1 in these cell lines. The results demonstrate that in normal and tumour-derived human oral keratinocytes, TGF-β1 signal transduction is not mediated by inositol phosphates or cAMP.

Original languageEnglish (US)
Pages (from-to)117-122
Number of pages6
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1315
Issue number2
DOIs
StatePublished - Mar 1 1996
Externally publishedYes

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Inositol Phosphates
Keratinocytes
Protein Isoforms
Neoplasms
Cell Line
Cell Surface Receptors
Bradykinin
Colforsin
Tumor Cell Line
Adenylyl Cyclases
Thymidine
Cell Differentiation
Signal Transduction
Up-Regulation
Ligands
Serum

Keywords

  • Cyclic AMP
  • Inositol phosphate
  • Isoform
  • Keratinocyte
  • Transforming growth factor-β

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

Cite this

TGF-β isoforms fail to modulate inositol phosphates and cAMP in normal and tumour-derived human oral keratinocytes. / Collier, Adam J.; Elsegood, Kathryn A.; Yeudall, William Andrew; Paterson, Ian C.; Prime, Stephen S.; Sandy, Jonathan R.

In: Biochimica et Biophysica Acta - Molecular Basis of Disease, Vol. 1315, No. 2, 01.03.1996, p. 117-122.

Research output: Contribution to journalArticle

Collier, Adam J. ; Elsegood, Kathryn A. ; Yeudall, William Andrew ; Paterson, Ian C. ; Prime, Stephen S. ; Sandy, Jonathan R. / TGF-β isoforms fail to modulate inositol phosphates and cAMP in normal and tumour-derived human oral keratinocytes. In: Biochimica et Biophysica Acta - Molecular Basis of Disease. 1996 ; Vol. 1315, No. 2. pp. 117-122.
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