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Effect of adenovirus-mediated PTEN gene on ulcerative colitis-associated colorectal cancer

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International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Purpose

This study investigated the expression pattern of PTEN and its effect on carcinogenesis of ulcerative colitis-associated colorectal cancer, leading to insights into the underlying molecular mechanism.

Methods

We established a mouse model of ulcerative colitis-associated colorectal cancer by treating the animals with azoxymethane (AOM) and dextran sulphate sodium (DSS), and investigated the inflammation–dysplasia–carcinoma sequence. Expression patterns of PTEN, p-Akt and Ki-67 were shown by immunohistochemistry; western blotting techniques were used to detect protein expression of PTEN, p-Akt and caspase 3; TUNEL assay was used to measure apoptosis in colon epithelial cells; and colorimetric analysis was able to determine MPO activity in colon tissues.

Results

During the inflammation–dysplasia–carcinoma sequence, PTEN expression gradually decreased, while p-Akt expression increased; PTEN and p-Akt levels were negatively correlated. Compared to the AOM-DSS and Ad-0 groups, Ad-PTEN mice had longer colons, fewer tumours (P < 0.01) and smaller tumour sizes (P < 0.05). After injecting Ad-PTEN, expression of p-Akt, Ki-67 and MPO activity decreased dramatically, whereas PTEN increased. The TUNEL assay showed increased apoptotic cells and caspase 3 expression in the Ad-PTEN group.

Conclusion

PTEN plays an important role in the inflammation–dysplasia–carcinoma sequence and may be a new molecular target in preventing and treating ulcerative colitis-associated colorectal cancer.

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Acknowledgments

The present work was supported by the National Science Foundation of China, Beijing (no. 30770983).

Conflicts of interest

The authors declared to have no conflicts of interest.

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Authors and Affiliations

  1. Department of Gastroenterology and Geriatrics Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China

    Zhi Li, Gong Xiang Liu, Yu Lan Liu, Xi Chen, Xiao Li Huang & Hua Tian Gan

  2. Department of Gastroenterology, Affiliated Hospital (T.C.M), Lu Zhou Medical College, Luzhou, Sichuan, China

    Zhi Li

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  1. Zhi Li
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Correspondence to Hua Tian Gan.

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Li, Z., Liu, G.X., Liu, Y.L. et al. Effect of adenovirus-mediated PTEN gene on ulcerative colitis-associated colorectal cancer. Int J Colorectal Dis 28, 1107–1115 (2013). https://doi.org/10.1007/s00384-013-1678-9

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