Yarbrough Wendell G, Whigham Amy, Brown Brandee, Roach Michael, Slebos Robbert
Department of Otolaryngology, Vanderbilt University, Nashville, TN 37232-8605, USA.
Int J Radiat Oncol Biol Phys. 2007;69(2 Suppl):S98-101. doi: 10.1016/j.ijrobp.2007.04.082.
To investigate phosphoinositide kinase-3 (PI3K) activation in relation to human papillomavirus (HPV) status in head and neck squamous cell carcinoma (HNSCC).
Gene expression microarray data were analyzed to determine differentially expressed genes between HPV(+) and HPV(-) HNSCC. PIK3CA gene expression was confirmed by quantitative reverse transcriptase-polymerase chain reaction in seven HPV(+) and seven HPV(-) primary HNSCCs. PIK3CA mutation status in three HPV(+) and nine HPV(-) cell lines was determined by polymerase chain reaction amplification of hot spot exons (1, 9, 20) followed by direct sequencing.
PIK3CA was overexpressed in HPV(+)-associated HNSCC compared with the expression in HPV(-) HNSCC. Activation of PIK3CA by mutation was found in 1 of the 12 tested HNSCC cell lines.
Activation of PI3K by mutation of PIK3CA is rare in HNSCC cell lines and was not found in three HPV(+) cell lines. One mechanism by which HPV-associated HNSCC might activate PI3K is increased expression of PIK3CA.
研究头颈部鳞状细胞癌(HNSCC)中磷酸肌醇激酶-3(PI3K)激活与人类乳头瘤病毒(HPV)状态的关系。
分析基因表达微阵列数据,以确定HPV(+)和HPV(-)HNSCC之间的差异表达基因。通过定量逆转录聚合酶链反应在7例HPV(+)和7例HPV(-)原发性HNSCC中证实PIK3CA基因表达。通过对热点外显子(1、9、20)进行聚合酶链反应扩增,然后直接测序,确定3例HPV(+)和9例HPV(-)细胞系中的PIK3CA突变状态。
与HPV(-)HNSCC中的表达相比,PIK3CA在HPV(+)相关的HNSCC中过表达。在12个测试的HNSCC细胞系中的1个中发现了通过突变激活的PIK3CA。
PIK3CA突变激活PI3K在HNSCC细胞系中很少见,在3个HPV(+)细胞系中未发现。HPV相关的HNSCC激活PI3K的一种机制可能是PIK3CA表达增加。