Epithelium maintains homeostasis by the signaling balance of growth stimulation and inhibition. Recently, loss of growth inhibitory effects of transforming growth factor-β(TGF-β) on epithelial cells is regarded as a possible mechanism of cancer. Although the genomic mutation in type I and type Ⅱ receptors of TGF-β is considered one of important mechanism of these inactivation, there might be another inactivation mechanism because the mutation rate is relatively low and inhibitory effect is not associated with the mutation. The purpose of this study is evaluating controlling mechanism type Ⅱ receptor of TGF-β by detecting effects of TGF-β on growth inhibition and on expression of cell cycle regulatory protein p21CIP1. Eight cancer cell lines derived from oral squamous cell carcinoma(OSCC) were examined. There was no growth inhibition effects by TGF-β except YD-8 cells. YD-8 cells which showed growth inhibition expresses p21CIP1 by TGF-β whether refractory cell lines, YD-9, did not. All of the tumor cells express mRNA of type Ⅱ receptor by RT-PCR and northern blot analysis, especially on YD-8 and YD-17M. From these results, most of oral cancer cell lines might loose the growth inhibitory effects by TGF-β, and the growth inhibition on YD-8 cells was mediated by expression of p21CIP1.

The imbalance between epithelial cell growth and inhibitory factors may cause human epithelial cancer. The dysregulation of growth inhibitory effect of TGF-β1 has been recognized in a variety of carcinomas. This study aimed to investigate the expression of TGF-β1 type II receptors(TβR-II) in the carcinogenesis of oral squamous cell carcinoma(OSCC). Six cell lines established from OSCC in the department of Oral Pathology, Yonsei University College of Dentistry were used. DNA was extracted from harvested cells by phenol-chloroform method. Polymerase chain reaction (PCR) was done with each primer of exon 3, 4, 5, 6 of TβR-II gene. PCR products were inserted to cloning vector (pGEM-T easy vector) and then analyzed to automatic DNA sequencing analyzer. Reverse transcriptase-PCR (RT-PCR) was performed to confirm the mRNA expression of TβR-II gene. Western blotting was performed to detect the expression of the TβR-II protein. As results, a frameshift within a polyadenine region of exon 3 was found in YD-8 cell line. In YD-17 cell line, a missense mutation at codon 238 of exon 4 was found, suggesting the alteration of amino acid from asparagine to aspartic acid. TβR-II mRNA was detected in all cancer cell lines, but it was slightly decreased as compared to that of normal oral mucosal cells. In Western blotting, no TβR-Ⅱ protein was detected in all OSCC cell lines. These results suggested that the altered regulation of TGF-β1 function might play a role in the development of OSCC.