Elevated Expression of Poly(ADP-Ribose) Polymerase-1 is Associated with Liver Metastasis in Colorectal Cancer.

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Activation of poly(ADP-ribose) polymerase-1 (PARP-1) and its subsequent cleavage are early markers of apoptosis. PARP-1 is associated with DNA repair and so chromosome stability, cell cycle regulation, as well as tumorigenesis. To investigate the role of PARP-1 expression in colorectal carcinoma and its metastasis of liver, we compared the expression of PARP-1 in primary colorectal cancers with (n=15) and without liver metastasis (n=17) using a semi-quantitative reverse transcription - polymerase chain reaction. We also examined the expressions of poly(ADP-ribose) (PAR) and p53 in these tumors by immunohistochemistry. A significantly higher PARP-1 mRNA expression was noted in tumors with liver metastasis than those without liver metastasis (p<0.01). Colorectal cancers positively stained for p53 exhibited significantly higher PARP-1 mRNA expression than p53-negative tumors (p<0.01). The PAR labeling index (LI) of tumors with metastasis (0.33 ﾂｱ 0.33) was not significantly different (p=0.35) from that of tumors without liver metastasis (0.38 ﾂｱ 0.19). p53-positive tumors tended to have higher PAR LI levels than p53-negative tumors (p=0.08). Our findings suggest that PARP-1 may contribute to liver metastasis due to its DNA repair activity, resulting in survival of the tumor cells with accumulation of metastaticrelated gene's damages. Detailed analysis of PARP-1 may be useful in cancer research and/or cancer therapy.
長崎大学の論文