Overexpression of poly(ADP-ribose) polymerase-1 (PARP-1) in the early stage of colorectal carcinogenesis

Eur J Cancer. 2006 Sep;42(14):2374-81. doi: 10.1016/j.ejca.2006.01.061. Epub 2006 Jun 30.


Colorectal carcinogenesis is initiated mainly by aberrant activation of the Wnt signaling pathway, caused by mutation of either APC or beta-catenin (CTNNB1) gene. Poly(ADP-ribose) polymerase-1 (PARP-1) is a highly conserved nuclear enzyme, which binds tightly to DNA and plays a role in DNA repair, recombination, proliferation and genomic stability. It has recently been shown that PARP-1 is a novel co-activator of TCF-4/beta-catenin-evoked gene transactivation and may play a role in colorectal carcinogenesis. The aim of this study was to examine the PARP-1 expression and determine whether it is correlated with the expression of beta-catenin and its target genes such as c-myc, cyclin D1 and matrix metalloproteinase (MMP)-7 in the early stage of sporadic colorectal carcinogenesis. Using the semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), 91 colorectal tumours, including 65 adenomas and 26 submucosal (pT1) cancers, were analysed for the expression of PARP-1, beta-catenin, c-myc, cyclin D1 and MMP-7. Immunohistochemical analysis of PARP-1 and beta-catenin was also performed. PARP-1 mRNA overexpression was detected in 64 (70.3%) of the 91 tumours. PARP-1 overexpression was significantly correlated with tumour size and histopathology. Overexpression of beta-catenin, c-myc, cyclin D1 and MMP-7 mRNA expression was observed in 39.6%, 78.0%, 83.5% and 72.5% of the 91 tumours, respectively. PARP-1 overexpression was correlated significantly with overexpression of beta-catenin, c-myc, cyclin D1 and MMP-7. Correlation of PARP-1 expression with beta-catenin overexpression was also demonstrated by immunohistochemistry. The results suggest that PARP-1, in conjunction with beta-catenin, c-myc, cyclin D1 and MMP-7, plays an important role in the early stage of colorectal carcinogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenoma / metabolism*
  • Colorectal Neoplasms / metabolism*
  • Cyclin D1 / metabolism
  • Female
  • Genes, myc
  • Humans
  • Immunohistochemistry / methods
  • Male
  • Matrix Metalloproteinase 7 / metabolism
  • Middle Aged
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases / metabolism*
  • Proto-Oncogene Proteins c-myc / metabolism
  • RNA, Messenger / metabolism
  • RNA, Neoplasm / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • beta Catenin / metabolism


  • Proto-Oncogene Proteins c-myc
  • RNA, Messenger
  • RNA, Neoplasm
  • beta Catenin
  • Cyclin D1
  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases
  • Matrix Metalloproteinase 7