Effects of transforming growth factor beta-1 on growth-regulatory genes in tumour-derived human oral keratinocytes.
This study examined the effect of transforming growth factor beta-1 (TGF-beta 1) on c-myc, RB1, junB and p53 expression together with pRb phosphorylation, in carcinoma-derived and normal human oral keratinocytes with a range of inhibitory responses to this ligand. Amplification of c-myc was observed in eight of eight tumour-derived cell lines and resulted in corresponding mRNA expression. The down-regulation of c-myc expression by TGF-beta 1 predominantly reflected growth inhibition by TGF-beta 1, but in two of eight tumour-derived cell lines which were partially responsive to TGF-beta 1 c-myc expression was unaltered by this ligand. While RB1 mRNA levels were unaltered by TGF-beta 1, the ligand caused the accumulation of the underphosphorylated form of the Rb protein in all cells irrespective of TGF-beta 1-induced growth arrest. junB expression was up-regulated by TGF-beta 1 in cells with a range of growth inhibitory responses. All cells contained mutant p53. TGF-beta 1 did not affect p53 mRNA expression in both tumour-derived and normal keratinocytes and there was no alteration in p53 protein levels in keratinocytes expressing stable p53 protein following TGF-beta 1 treatment. The data indicate that TGF-beta-induced growth control can exist independently of the presence of mutant p53 and the control of Rb phosphorylation and c-myc down-regulation. It may be that TGF-beta growth inhibition occurs via multiple mechanisms and that the loss of one pathway during tumour progression does not necessarily result in the abrogation of TGF-beta-induced growth control.
Paterson
I C
IC
Department of Oral and Dental Science, University of Bristol Dental Hospital and School, UK.
Patel
V
V
Sandy
J R
JR
Prime
S S
SS
Yeudall
W A
WA
D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D002478:Cells, Cultured; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D016758:Genes, jun / Q000187:drug effects; D016259:Genes, myc / Q000187:drug effects; D016158:Genes, p53 / Q000187:drug effects; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D009062:Mouth Neoplasms / Q000235:genetics* / Q000473:pathology; D010766:Phosphorylation; D016160:Retinoblastoma Protein / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D016160:Retinoblastoma Protein; D016212:Transforming Growth Factor beta