Cyclin D1 amplification is independent of p16 inactivation in head and neck squamous cell carcinoma

被引:67
作者
Okami, K
Reed, AL
Cairns, P
Koch, WM
Westra, WH
Wehage, S
Jen, J
Sidransky, D
机构
[1] Johns Hopkins Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Div Head & Neck Canc Res, Baltimore, MD 21205 USA
[2] Johns Hopkins Hosp, Dept Pathol, Baltimore, MD 21287 USA
[3] Yamaguchi Univ, Dept Otolaryngol, Ube, Yamaguchi 755, Japan
关键词
cyclin D-1; p16; head and neck cancer;
D O I
10.1038/sj.onc.1202837
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Progression through the G(1) phase of the cell cycle is mediated by phosphorylation of the retinoblastoma protein (pRb) resulting in the release of essential transcription factors such as E2F-1. The phosphorylation of pRb is regulated positively by cyclin D-1/CDK4 and negatively by CDK inhibitors, such as p16 (CDKN2/MTS-1/INK4A), The p16/cyclin D-1/Rb pathway plays a critical role in tumorigenesis and many tumor types display a high frequency of inactivation of at least one component of this pathway. In order to determine the overall contribution of these three components to progression of head and neck squamous cell carcinoma (HNSCC), we examined p16 inactivation, cyclin D-1 amplification, and pRb expression in 23 primary HNSCC tumors and five cell lines, p16 inactivation was detected in 19/23 (83%) primary tumors by detailed genetic analysis and was confirmed by immunohistochemistry (MC), Absence of Ph protein expression indicative of pRb inactivation was identified in 2/23 (9%) tumors, In this set of tumors, there was a perfect inverse correlation between p16 and pRb inactivation, Using fluorescence in situ hybridization (FISH) cyclin D-1 amplification was identified in 4/5 (80%) cell lines and 4/11 (36%) primary tumors. However, 2/4 cell lines and all four primary tumors with cyclin D-1 amplification contained a concomitant alteration of p16, Therefore 21/23 (91%) of primary HNSCC contained at least one alteration in the p16/cyclin D-1/Rb pathway. Although p16 and Rb alteration are apparently exclusive, cyclin D-1 amplification occurs concomitantly with the loss of p16 suggesting an additional role for this amplification in HNSCC.
引用
收藏
页码:3541 / 3545
页数:5
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