PARP-1 Expression is Increased in Colon Adenoma and Carcinoma and Correlates with OGG1

Abstract

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.

PARP‐1 regulates DNA repair factor availability

“…Additionally, these observations align with studies demonstrating that PARP‐1 and PAR are elevated in PCa compared to benign prostatic hyperplasia in a Chinese cohort (Wu et al , ) and that PARP‐1 protein is elevated in cases of primary PCa as compared to normal controls (Salemi et al , ). In other tumor types, elevated PARP‐1 mRNA is associated with poor prognosis in gliomas (Li et al , ), PARP‐1 mRNA is elevated in colon carcinoma when compared to adenoma (Dziaman et al , ), PARP‐1 gene expression is associated with lymph node spread of malignant pleural mesothelioma (Walter et al , ), and PARP‐1 mRNA and protein are elevated in endometrial adenocarcinoma (Bi et al , ). Both PARP‐1 mRNA and protein are highly expressed in small cell lung cancer (Byers et al , ), but PARP‐1 protein has been shown to associate with longer PFS in limited‐stage small cell lung cancer (Kim et al , ).…”

WITHDRAWN: An analysis of the gene interaction networks identifying the role of PARP1 in metastasis of non-small cell lung cancer

“…PARP1 played an important role in DNA damage repair, [15][16][17], which made PARP1 a valuable therapeutic target in the research of disease drug. Recently, it was found that PARP1 presented high expression in a series of cancers, which provided a high-value target for the study of tumor detection, stage and biological characteristics [18][19][20][21][22][23]. The overexpression of PARP1 results from much DNA damage in cancer cells with unstable genes, instead of the induction of the activated specific carcinogenic pathway [24].…”

pSTAT5 and ERK exhibit different expression in myeloproliferative neoplasms

“…Interpretation of IhC staining was performed as described in detail earlier (28,29). Remmele and Stegner (30) scoring system was used.…”