TY - JOUR
T1 - TGF-β isoforms fail to modulate inositol phosphates and cAMP in normal and tumour-derived human oral keratinocytes
AU - Collier, Adam J.
AU - Elsegood, Kathryn A.
AU - Yeudall, W. Andrew
AU - Paterson, Ian C.
AU - Prime, Stephen S.
AU - Sandy, Jonathan R.
N1 - Funding Information:
The study was supportedb y an MRC Project Grant (G 9123775 SD) and Denman'sC haritableT rust.
PY - 1996/3/1
Y1 - 1996/3/1
N2 - 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.
AB - 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.
KW - Cyclic AMP
KW - Inositol phosphate
KW - Isoform
KW - Keratinocyte
KW - Transforming growth factor-β
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U2 - 10.1016/0925-4439(95)00109-3
DO - 10.1016/0925-4439(95)00109-3
M3 - Article
C2 - 8608168
AN - SCOPUS:0029670278
SN - 0925-4439
VL - 1315
SP - 117
EP - 122
JO - Biochimica et Biophysica Acta - Molecular Basis of Disease
JF - Biochimica et Biophysica Acta - Molecular Basis of Disease
IS - 2
ER -