Park Hun-Woong, Song Si-Youn, Lee Tae-Jin, Jeong Daewon, Lee Tae-Yoon
Department of Otolaryngology, College of Medicine, Yeungnam University, Daegu 705-717, Korea.
Oncol Rep. 2007 Jul;18(1):267-72.
In the present study, we analyzed p16, retinoblastoma (Rb), and cyclin D1 abnormalities in head and neck squamous cell carcinoma (HNSCC) tissues and cell lines from Korean patients. We found a 40% loss of heterozygosity at the D9S171 locus (9p21 region) these tissues. All eight of the HNSCC cell lines did not express the p16 protein, and in two of these cell lines (Amc-HN-6 and 8), this was due to a deletion of the p16 gene. Three of the cell lines (Amc-HN-3 to 5) that expressed the p16 mRNA had the same nonsense mutation at codon 50 (CGA-Arg to TGA-Ter). The Amc-HN-1 and Amc-HN-7 cell lines, which did not express the p16 mRNA, had a missense mutation at codon 9 (GCC-Ala to GTC-Val) and a silent mutation at codon 106 (CCC-Pro to CCA), respectively. The Amc-HN-2 cell line (p16 exon-positive/mRNA-negative) had a single base deletion at codon 38 (CGG-Arg to CG), which resulted in a frameshift and a consequent stop signal at codon 44. The Rb protein was detected in all of the eight cell lines, although it was inactive in five of these due to hyperphosphorylation. The inverse relationship between p16 and Rb was 62.5% (5/8). Cyclin D1 was overexpressed in all of the eight cell lines. Our results suggest that the abrogation of p16, the overexpression of cyclin D1, and the consequent inactivation of Rb could be important factors in the carcinogenesis of HNSCCs.
在本研究中，我们分析了韩国患者头颈部鳞状细胞癌（HNSCC）组织和细胞系中的p16、视网膜母细胞瘤（Rb）和细胞周期蛋白D1异常情况。我们发现这些组织在D9S171位点（9p21区域）存在40%的杂合性缺失。所有8种HNSCC细胞系均不表达p16蛋白，其中2种细胞系（Amc-HN-6和8）是由于p16基因缺失所致。3种表达p16 mRNA的细胞系（Amc-HN-3至5）在密码子50处发生相同的无义突变（CGA-Arg突变为TGA-Ter）。不表达p16 mRNA的Amc-HN-1和Amc-HN-7细胞系分别在密码子9处发生错义突变（GCC-Ala突变为GTC-Val）和在密码子106处发生沉默突变（CCC-Pro突变为CCA）。Amc-HN-2细胞系（p16外显子阳性/mRNA阴性）在密码子38处发生单碱基缺失（CGG-Arg突变为CG），导致移码并在密码子44处产生终止信号。所有8种细胞系中均检测到Rb蛋白，尽管其中5种因过度磷酸化而失活。p16与Rb之间的负相关率为62.5%（5/8）。所有8种细胞系中细胞周期蛋白D1均过度表达。我们的结果表明，p16缺失、细胞周期蛋白D1过度表达以及随之而来的Rb失活可能是HNSCC发生癌变的重要因素。
