Simultaneous down-regulation of tumor suppressor genes RBSP3/CTDSPL, NPRL2/G21 and RASSF1A in primary non-small cell lung cancer.
Simultaneous down-regulation of tumor suppressor genes RBSP3/CTDSPL, NPRL2/G21 and RASSF1A in primary non-small cell lung cancer.
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DOI：
10.1186/1471-2407-10-75
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发表时间：
2010-03-01
期刊：
影响因子：
3.8
通讯作者：
Zabarovsky ER
中科院分区：
文献类型：
--
作者：
Senchenko VN;Anedchenko EA;Kondratieva TT;Krasnov GS;Dmitriev AA;Zabarovska VI;Pavlova TV;Kashuba VI;Lerman MI;Zabarovsky ER
人类3号染色体的短臂与包括肺癌在内的许多癌症的发展有关。在3p21.3区域发现了3个真正的肺癌抑癌基因，即RBSP 3（AP 20区域）、NPRL 2和RASSF 1A（LUCA区域）。我们以前的研究表明，AP 20和LUCA亚区的纯合性缺失常发生在同一肿瘤中（P < 10-6）。采用实时荧光定量RT-PCR技术检测了59例原发性非小细胞肺癌组织中RBSP 3、NPRL 2、RASSF 1A、GAPDH、RPN 1 mRNA和RBSP 3 DNA拷贝数，其中鳞癌41例，腺癌18例。本研究旨在探讨非小细胞肺癌组织中mRNA水平与临床病理特征的关系。在肿瘤发展的早期发现所有三种基因的表达显著降低（≥2）：在85%的病例中RBSP 3、73%的病例中NPRL 2和67%的病例中RASSF 1A（P < 0.001），在鳞状细胞中比在腺癌中更显著。在100%已经处于鳞状细胞癌I期的病例中观察到NPRL 2和RBSP 3两者的强烈抑制。RASSF 1A表达异常与鳞癌（P = 0.196）和腺癌（P < 0.05）的肿瘤进展相关。最有可能的是，遗传和表观遗传机制可能是非小细胞肺癌中RBSP 3转录失活的原因，因为根据NotI微阵列数据，在80%的鳞状细胞癌和38%的腺癌中检测到RBSP 3启动子甲基化。使用NotI微阵列，我们测试了LUCA（NPRL 2，RASSF 1A）和AP 20（RBSP 3）区域在同一肿瘤样品中缺失或甲基化的频率，发现这发生在所有研究样品的39%中（P < 0.05）。我们的数据支持这一假设，这些TSG参与了非小细胞肺癌的肿瘤发生。遗传和表观遗传机制都有助于这三个基因的下调，代表3p21.3中的两个肿瘤抑制簇。最重要的是RBSP 3、NPRL 2和RASSF 1A在同一原发性NSCLC样本中同时表达降低：在39%的病例中，这三种基因均显示表达降低（P < 0.05）。
The short arm of human chromosome 3 is involved in the development of many cancers including lung cancer. Three bona fide lung cancer tumor suppressor genes namely RBSP3 (AP20 region),NPRL2 and RASSF1A (LUCA region) were identified in the 3p21.3 region. We have shown previously that homozygous deletions in AP20 and LUCA sub-regions often occurred in the same tumor (P < 10-6). We estimated the quantity of RBSP3, NPRL2, RASSF1A, GAPDH, RPN1 mRNA and RBSP3 DNA copy number in 59 primary non-small cell lung cancers, including 41 squamous cell and 18 adenocarcinomas by real-time reverse transcription-polymerase chain reaction based on TaqMan technology and relative quantification. We evaluated the relationship between mRNA level and clinicopathologic characteristics in non-small cell lung cancer. A significant expression decrease (≥2) was found for all three genes early in tumor development: in 85% of cases for RBSP3; 73% for NPRL2 and 67% for RASSF1A (P < 0.001), more strongly pronounced in squamous cell than in adenocarcinomas. Strong suppression of both, NPRL2 and RBSP3 was seen in 100% of cases already at Stage I of squamous cell carcinomas. Deregulation of RASSF1A correlated with tumor progression of squamous cell (P = 0.196) and adenocarcinomas (P < 0.05). Most likely, genetic and epigenetic mechanisms might be responsible for transcriptional inactivation of RBSP3 in non-small cell lung cancers as promoter methylation of RBSP3 according to NotI microarrays data was detected in 80% of squamous cell and in 38% of adenocarcinomas. With NotI microarrays we tested how often LUCA (NPRL2, RASSF1A) and AP20 (RBSP3) regions were deleted or methylated in the same tumor sample and found that this occured in 39% of all studied samples (P < 0.05). Our data support the hypothesis that these TSG are involved in tumorigenesis of NSCLC. Both genetic and epigenetic mechanisms contribute to down-regulation of these three genes representing two tumor suppressor clusters in 3p21.3. Most importantly expression of RBSP3, NPRL2 and RASSF1A was simultaneously decreased in the same sample of primary NSCLC: in 39% of cases all these three genes showed reduced expression (P < 0.05).
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影响因子：
3.5
作者：
Li, JF;Protopopov, AI;Zabarovsky, ER
通讯作者：
Zabarovsky, ER
影响因子：
30.8
作者：
Dammann, R;Li, C;Pfeifer, GP
通讯作者：
Pfeifer, GP
影响因子：
3.7
作者：
Mitra, Sraboni;Indra, Dipanjana Mazumder;Panda, Chinmay K.
通讯作者：
Panda, Chinmay K.
影响因子：
8
作者：
Li, JF;Wang, FL;Zabarovsky, E
通讯作者：
Zabarovsky, E
影响因子：
1.2
作者：
Anedchenko, E. A.;Kisseljova, N. P.;Senchenko, V. N.
通讯作者：
Senchenko, V. N.