TGF-beta isoforms fail to modulate inositol phosphates and cAMP in normal and tumour-derived human oral keratinocytes.
This study examined inositol phosphate and cAMP regulation by TGF-beta 1, -beta 2 and -beta 3 in normal and tumour-derived human oral keratinocytes. Previous findings indicated that the cell lines expressed TGF-beta cell surface receptors and had a range of response to exogenous TGF-beta 1, -beta 2 and -beta 3 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-beta 1, as measured previously by thymidine incorporation. Treatment of cells with bradykinin or serum caused up-regulation of inositol phosphate levels; by contrast, TGF-beta 1, -beta 2 and -beta 3 failed to modulate inositol phosphates. In two tumour-derived cell lines, the TGF-beta 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-beta in these cells lines. The results demonstrate that in normal and tumour-derived human oral keratinocytes, TGF-beta signal transduction is not mediated by inositol phosphates or cAMP.
Collier
A J
AJ
Department of Oral and Dental Science, University of Bristol, UK.
Elsegood
K A
KA
Yeudall
W A
WA
Paterson
I C
IC
Prime
S S
SS
Sandy
J R
JR
D001920:Bradykinin / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000187:drug effects; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism*; D008544:Melanocytes / Q000187:drug effects / Q000378:metabolism*; D009061:Mouth Mucosa / Q000378:metabolism; D009062:Mouth Neoplasms / Q000378:metabolism*; D012016:Reference Values; D013936:Thymidine / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D007295:Inositol Phosphates; D016212:Transforming Growth Factor beta; D004247:DNA; D000242:Cyclic AMP; D001920:Bradykinin; D013936:Thymidine