DNA methylation and expression of p16INK4A gene in pulmonary adenocarcinoma and anthracosis in background lung
DNA methylation and expression of p16INK4A gene in pulmonary adenocarcinoma and anthracosis in background lung
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背景肺肺腺癌和炭疽病中p16INK4A基因的DNA甲基化和表达
DOI：
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发表时间：
1999
影响因子：
6.4
通讯作者：
M. Noguchi
中科院分区：
文献类型：
--
作者：
M. Hou;Y. Morishita;Tatsuo Iljima;Y. Inadome;K. Mase;Yuichi Dai;M. Noguchi
p16（CDKN 2/MTS-1/INK 4A）肿瘤抑制基因在肺癌中经常因DNA甲基化而失活。为了阐明背景炭疽病是否可能在DNA甲基化和p16基因失活中发挥作用，我们通过甲基化特异性聚合酶链反应检测了p16启动子区域的DNA甲基化，并通过化学方法检测了p16表达，并将结果与通过原始定量方法测量的背景炭疽病水平进行了比较。尸检时，在死于肺腺癌的患者的6/19个肿瘤（32%）中观察到p16基因的DNA甲基化。有p16基因甲基化的病例的背景炭疽病程度（外源性致癌因素的影响）（平均吸光度值，A = 0.715）显著高于无甲基化的病例（平均A值= 0.298）。在所有p16基因甲基化的肿瘤中，p16表达失活。p16正常表达组黑尘物质沉积的平均A值（A = 0.151）显著低于p16异常表达组（A = 0.531）。这些结果表明，背景炭疽病的水平与肺腺癌发生中p16表达的失活以及p16基因启动子区域的DNA甲基化密切相关。国际癌症杂志（Pred. Oncol.）84：609-613，1999.© 1999 Wiley利斯公司
The p16 (CDKN2/MTS‐1/INK4A) tumor‐suppressor gene is frequently inactivated by DNA methylation in lung carcinomas. To clarify whether background anthracosis may play a role in DNA methylation and inactivation of the p16 gene, we examined DNA methylation of the p16‐promoter region by methylation‐specific polymerase chain reaction, and p16 expression immunohistochemically, and compared the results with the level of background anthracosis which was measured by an original quantitative method. At autopsy, DNA methylation of the p16 gene was observed in 6/19 tumors (32%) from patients who had died of pulmonary adenocarcinoma. The degree of background anthracosis (the effect of extrinsic carcinogenic factors) (mean absorbance value, A = 0.715) of the cases with p16‐gene methylation was significantly higher than that without methylation (mean A value = 0.298). p16 expression was inactivated in all tumors with p16‐gene methylation. The mean A value of black dust matter deposition in cases with normal expression of p16 (A = 0.151) was significantly lower than cases with abnormal expression of p16 (A = 0.531). These results indicate that the level of background anthracosis is closely associated with inactivation of p16 expression and also DNA methylation of the p16‐gene promoter region in pulmonary adenocarcinogenesis. Int. J. Cancer (Pred. Oncol.) 84:609–613, 1999. © 1999 Wiley‐Liss, Inc.
DOI：
10.1073/pnas.93.18.9821
发表时间：
1996-09-03
影响因子：
11.1
作者：
Herman, JG;Graff, JR;Baylin, SB
通讯作者：
Baylin, SB
DOI：
10.1073/pnas.87.12.4533
发表时间：
1990-06-01
影响因子：
11.1
作者：
FRAGA, CG;SHIGENAGA, MK;AMES, BN
通讯作者：
AMES, BN
人类乳腺癌中 p16（INK4A）异常表达的频率很高。
DOI：
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发表时间：
1996
期刊：
The American journal of pathology.
影响因子：
--
作者：
Geradts,J;Wilson,PA
通讯作者：
Wilson,PA