头颈部鳞癌中端粒酶活性与调节蛋白p16、CyclinD1和pRb表达的关系

TELOMERASE ACTIVITY,CELL CYCLE REGULATORY PROTEINS P16 CYCLIND1 AND PRB IN HUMAN HEAD AND NECK SQUAMOUS CELL CARCINOMA

目的:探讨端粒酶活性与细胞周期调节蛋白p16、CyclinD1和pRb的关系。方法:采用TRAP-PCR-ELISA法对32例原发头颈部鳞癌组织进行端粒酶活性检测,并应用免疫组织化学方法检测细胞周期调节蛋白p16、CyclinD1和pRb的表达。结果:32例原发头颈部鳞癌中,有27例端粒酶活化,阳性率为84.4%。p16、CyclinD1、pRb的总异常率为90.6%(29/32),其中p16和pRb蛋白表达缺失分别为62.5%(20/32)和34.4%(11/32),CyclinD1过表达为34.4%(11/32)。p16与pRb呈负相关性(P<0.01)。端粒酶活性与细胞周期调节蛋白p16、CyclinD1和pRb总异常无相关性;端粒酶活性与p16、CyclinD1和pRb两两之间无相关性;p16、pRb的表达组与失活组端粒酶活性值无统计学差异,CyclinD1的正常表达组和过表达组端粒酶活性值无差异;但按照p16、CyclinD1和pRb表达不同将32例标本分成八组后,分析发现p16+/pRb-/CyclinD1过表达组端粒酶活性值明显高于其它组,其余各组间无统计学差异(P>0.05)。结论:端粒酶活化与头颈部鳞癌的发生发展有密切关系。p16/CyclinD1/pRb通路异常与HNSCC的发病机制密切相关。头颈部鳞癌中端粒酶活性与p16、CyclinD1和pRb的确切关系有待深入研究。

Objective：To explore the relationship between telomerase activity and cell cycle regulatory proteins pl6 , CyclinD1 and pRb in human head and neck squamous cell carcinomas. Methods：Thirty- two patient samples of primary head and neck squamous cell carcinoma were using TRAP - PCR - ELISA for detection of telomer- ase activity. Immunohistochemistry was employed to detect the expression of pl6 , CyclinD1 and pRb in 32 primary tumors. Results： Twenty - seven of 32 （ 84.4% ） cancer samples were telomerase positive . A total of 29/32 （90. 6% ）of primary HNSCC contained at least one alteration in the pl6/CyclinD1/pRb pathway . The absence of pl6 and pRb expression was identified in 20/32 （62.5%）and 11/32（34.4% ）tumors respectively . Overexpression of CyclinD1 protein was detected in 11/32（34.4% ）HNSCC . No correlations were founded between telomerase activity and cell cycle regulatory proteins （pl6, CyclinD1 and pRb） ,although the levels of telomerase activity in specimens with positive pl6, negative pRb and overexpression of CyclinD1 were higher than those with the other expression spectrums of cell cycle regulatory proteins . Conclusion： Telomerase activation is consistent with the concept of telomerase playing a key role in tumorigenesis of head and neck squamous cell carcinoma. Alteration in at least one of cell cycle regulatory proteins pl6 , CyclinD1 and pRb might be required for most HNSCC development and progression. No clear relations are determined between telomerase activity and cell cycle regulatory proteins pl6, Cy- clinD1 and pRb.