Spindle assembly checkpoint and centrosome abnormalities in oral cancer.

Like many solid tumours, oral squamous cell carcinomas (OSCC) invariably exhibit chromosomal instability (CIN) leading to aneuploidy. The mechanisms responsible for CIN in OSCC, however, are largely unknown. This study examined the fidelity of the spindle checkpoint, together with the number, structure and function of centrosomes in a series of well-characterised aneuploid immortal OSCC-derived cell lines that harbour p53 and p16(INK4A) defects.

Induction of an epithelial to mesenchymal transition in human immortal and malignant keratinocytes by TGF-beta1 involves MAPK, Smad and AP-1 signalling pathways.

Recent data indicate that transforming growth factor-beta1 (TGF-beta1) can act to promote tumour progression in the late stages of carcinogenesis. The mechanism by which this occurs is unknown although a ligand-induced epithelial-mesenchymal transition (EMT) is thought to be important. In this study, we demonstrate that active Ras is required for TGF-beta1-induced EMT in human keratinocytes and that epidermal growth factor (EGF) can substitute for mutant Ras.

Attenuated type II TGF-beta receptor signalling in human malignant oral keratinocytes induces a less differentiated and more aggressive phenotype that is associated with metastatic dissemination.

We examined the effect of stable transfection of dominant negative TbetaR-II (dn TbetaR-II) cDNA in a human oral carcinoma cell line that contained normal Ras and was growth inhibited by TGF-beta1. Two clonal cell lines containing dn TbetaR-II were isolated and compared to the vector-only control and parent cell line. The treatment of cells with exogenous TGF-beta1 resulted in a decrease in ligand-induced growth inhibition and loss of c-myc downregulation in test cells compared to controls; transcriptional activation of certain genes including fra-1 and collagenase was retained.

TGF-beta1 acts as a tumor suppressor of human malignant keratinocytes independently of Smad 4 expression and ligand-induced G(1) arrest.

This study examined the role of TGF-beta1 in human keratinocyte malignancy. Two carcinoma-derived human oral keratinocyte cell lines, BICR 31 and H314, were selected on the basis of their known resistance to TGF-beta1-induced G(1) arrest, the presence of wild type TGF-beta cell surface receptors and normal Ras. Smad 4 protein was undetectable in both cell lines, but Smad 2 and Smad 3 were expressed at levels comparable with a fully TGF-beta responsive cell line, and treatment of the cells with TGF-beta1 resulted in the phosphorylation of Smad 2.