PARP-1 expression is increased in colon adenoma and carcinoma and correlates with OGG1.
PARP-1 expression is increased in colon adenoma and carcinoma and correlates with OGG1.
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DOI：
10.1371/journal.pone.0115558
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Olinski R
中科院分区：
文献类型：
--
作者：
Dziaman T;Ludwiczak H;Ciesla JM;Banaszkiewicz Z;Winczura A;Chmielarczyk M;Wisniewska E;Marszalek A;Tudek B;Olinski R
结肠癌的病理学在很大程度上取决于炎症驱动的氧化应激。对健康对照（138个个体）、良性腺瘤患者（AD，137个个体）和恶性癌患者（CRC，169个个体）的白细胞DNA中的8-氧代脱氧鸟苷（8-oxodGuo）水平的分析揭示，与对照相比，AD和CRC患者的白细胞DNA中的8-oxodGuo水平显著增加。其中OGG 1和PARP-1起着关键作用。我们研究了从AD和CRC患者获取的病变组织和边缘组织、正常组织以及从患者和健康受试者获取的白细胞中PARP-1和OGG 1 mRNA和蛋白的水平。在结肠肿瘤中，PARP-1 mRNA水平高于未受影响的结肠组织和息肉组织。PARP-1和OGG 1 mRNA水平在所有研究组织中均呈高度正相关。这表明PARP-1和OGG 1对其表达和稳定性的相互影响，并可能有助于结肠癌的进展。与正常结肠组织相比，息肉和CRC中的PARP-1和OGG 1蛋白水平高出数倍。携带OGG 1的Cys 326 Cys基因型的个体的特征是在患病组织中PARP-1蛋白水平高于Ser 326 Cys和Ser 326 Ser基因型。上述结果可能表明，具有多态性OGG 1的病变细胞募集更多的PARP蛋白，这是去除8-oxodGuo所必需的。因此，OGG 1活性降低/OGG 1基因多态性和8-oxodGuo水平较高的患者可能对PARP-1抑制剂治疗更敏感。
The ethiology of colon cancer is largely dependent on inflammation driven oxidative stress. The analysis of 8-oxodeoxyguanosine (8-oxodGuo) level in leukocyte DNA of healthy controls (138 individuals), patients with benign adenomas (AD, 137 individuals) and with malignant carcinomas (CRC, 169 individuals) revealed a significant increase in the level of 8-oxodGuo in leukocyte DNA of AD and CRC patients in comparison to controls. The counteracting mechanism is base excision repair, in which OGG1 and PARP-1 play a key role. We investigated the level of PARP-1 and OGG1 mRNA and protein in diseased and marginal, normal tissues taken from AD and CRC patients and in leukocytes taken from the patients as well as from healthy subjects. In colon tumors the PARP-1 mRNA level was higher than in unaffected colon tissue and in polyp tissues. A high positive correlation was found between PARP-1 and OGG1 mRNA levels in all investigated tissues. This suggests reciprocal influence of PARP-1 and OGG1 on their expression and stability, and may contribute to progression of colon cancer. PARP-1 and OGG1 proteins level was several fold higher in polyps and CRC in comparison to normal colon tissues. Individuals bearing the Cys326Cys genotype of OGG1 were characterized by higher PARP-1 protein level in diseased tissues than the Ser326Cys and Ser326Ser genotypes. Aforementioned result may suggest that the diseased cells with polymorphic OGG1 recruit more PARP protein, which is necessary to remove 8-oxodGuo. Thus, patients with decreased activity of OGG1/polymorphism of the OGG1 gene and higher 8-oxodGuo level may be more susceptible to treatment with PARP-1 inhibitors.
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影响因子：
29.4
作者：
Idogawa, M;Yamada, T;Hirohashi, S
通讯作者：
Hirohashi, S
影响因子：
3.7
作者：
Fekete A;Kenesi E;Hunyadi-Gulyas E;Durgo H;Berko B;Dunai ZA;Bauer PI
通讯作者：
Bauer PI
影响因子：
4.4
作者：
Hawthorn, L.;Lan, L.;Mojica, W.
通讯作者：
Mojica, W.
影响因子：
5.5
作者：
Duan, Yuntao;Gross, Robert A.;Sheu, Shey-Shing
通讯作者：
Sheu, Shey-Shing
DOI：
10.1016/j.mrfmmm.2011.02.009
发表时间：
2011-05-10
影响因子：
2.3
作者：
Janik, Justyna;Swoboda, Maja;Speina, Elzbieta
通讯作者：
Speina, Elzbieta