Aberrant Genetic Changes in Lung Cancer : p16^<INK4a> and p14^<ARF>

肺癌中的异常基因变化：p16^<INK4a> 和 p14^<ARF>

• 批准号: 13671398
• 负责人: YAMAKAWA Yosuke
• 金额: $ 2.3万
• 依托单位: Nagoya City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671398/
• 关键词: CDKN2; p16^<INK4a>; p14^<ARF>; lung cancer; p16; p14; pRb; p53

The CDKN2 gene on the short arm of chromosome 9p encodes two different cell cycle regulatory proteins, p16^<INK4a> and ARF. P16^<INK4a> and p14^<ARF> play an important role in independent cell cycle regulatory pathways, the retinoblastoma pathway and the p53 pathway, respectively. We have examined the expression of p16^<INK4a> and p14^<ARF> using competitive RT-PCR in 60 NSCLCs and matching normal lung tissues. The intensities of bands for p16^<INK4a> and p14^<ARF> were nearly equal or the intensity of p16^<INK4a> band slightly exceeded that of p14^<ARF> in the normal lung tissues (n=60). In 38 tumors the intensity of p16^<INK4a> band was similar to or slightly weaker than that of p14^<ARF>. In 6 tumors the intensity of p16^<INK4a> band was weaker than that of p14^<ARF>. In 15 tumors the intensity of p14^<ARP> band was very strong and p16^<INK4a> band was barely visible. In only one tumor the intensity of p16^<INK4a> band was very strong, while the band of p14^<ARF> was barely visible. The ratio of the intensity of p16^<INK4a> to p14^<ARF> band had an interesting correlation with the tumor's clinicopathological characteristics. The p stage II-IV tumors had significantly lower p16^<INK4a> to p14^<ARF> ratios than the p stage I tumors (p=0.036). The T2-4 tumors had significantly lower p16^<INK4a> to p14^<ARF> ratios than the T1 tumors (p=0.005). The N1-3 tumors had significantly lower p16^<INK4a> to p14^<ARF> ratios than the N0 tumors (p=0.014). Our results suggest that the ratio of expression of p16^<INK4a> to p14^<ARF> tends to decrease during the progression of NSCLC.

染色体9p短臂上的CDKN2基因编码两种不同的细胞周期调节蛋白p16^<INK4a>和ARF。P16^<INK4a>和p14^<ARF>分别在独立的细胞周期调控通路、视网膜母细胞瘤通路和p53通路中发挥重要作用。我们使用竞争性RT-PCR检测了60例非小细胞肺癌和匹配的正常肺组织中p16^<INK4a>和p14^<ARF>的表达。正常肺组织p16^<INK4a>和p14^<ARF>波段强度基本相等或p16^<INK4a>波段强度略高于p14^<ARF>波段（n=60）。38例肿瘤中，p16^<INK4a>条带强度与p14^<ARF>相似或略弱。在6例肿瘤中，p16^<INK4a>波段的强度弱于p14^<ARF>。15例肿瘤中p14^<ARP>波段强度很强，p16^<INK4a>波段几乎不可见。仅有1例肿瘤p16^<INK4a>波段强度非常强，而p14^<ARF>波段几乎不可见。p16^<INK4a>与p14^<ARF>频带的强度之比与肿瘤的临床病理特征有有趣的相关性。p期肿瘤的p16^<INK4a>和p14^<ARF>比值明显低于p期肿瘤（p=0.036）。T2-4肿瘤的p16^<INK4a>和p14^<ARF>比值明显低于T1肿瘤（p=0.005）。N1-3肿瘤的p16^<INK4a>和p14^<ARF>比值明显低于N0肿瘤（p=0.014）。我们的研究结果表明，在NSCLC的进展过程中，p16^<INK4a>与p14^<ARF>的表达比例呈下降趋势。

项目成果

森山 悟: "Ratio of Expression of p16^<INK4a> to p14^<ARF> Covelates with the Progression of Non-small Cell Lung Cancer"Jpn. J. Cancer. Res.. 93. 783-788 (2002)

Satoru Moriyama：“p16^<INK4a>与p14^<ARF>的表达比率与非小细胞肺癌的进展相关”J.Cancer Res. 93. 783-788 (2002)