Single alteration of p53 or E-cadherin genes can alter the surgical resection benefit in an experimental model of colon cancer

M. Pocard*, P. Debruyne, R. Bras-Gonçalves, M. Mareel, B. Dutrillaux, M. F. Poupon

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

PURPOSE: p53 and E-cadherin mutations are associated with a high risk of metastatic potential and local recurrence after colorectal surgery. LoVo, a human colon cancer cell line expressing a wild-type p53 and a normal E-cadherin, was studied. Clone LoVo-XC17 was obtained from LoVo cells transfected with a vector bearing a p53 273his mutation. Clone LoVo-92R4 was obtained from LoVo by culture cells with an E-cadherin down-regulation. LoVo, LoVo-XC17, and LoVo-92R4 were studied for in vivo behavior in a surgical intracolonic graft model. METHODS: Ten nude mice were used per cell line. A colonic tumor was obtained by tumor implantation into the cecal wall. The cecal tumor was resected at Day 15; at this time the volumes of the different tumors were similar. RESULTS: Surgical resection of the LoVo tumor led to 100 percent disease-free animals at one month. Surgical resection of mice grafted with the LoVo-XC17 line did not cure any mice (0/10; P = 0.001). Mice had local recurrences (10/10), mesenteric lymph node metastases (9/10), liver metastases (2/10), and peritoneal carcinomatosis (8/10). Surgical resection of LoVo-92R4 tumors led to cures in 30 percent (3/10), whereas 70 percent had isolated mesenteric lymph node metastases (7/10; P = 0.003). CONCLUSION: In this model surgical tumor resection was consistently effective for colonic tumors with functional p53 and E-cadherin, it was consistently ineffective with tumors displaying a mutated p53, and it was partially effective with E-cadherin-deficient tumors. This study shows that the alteration of a single gene can be associated with a profound alteration of surgical resection benefit.

Original languageEnglish
Pages (from-to)1106-1112
Number of pages7
JournalDiseases of the Colon and Rectum
Volume44
Issue number8
DOIs
Publication statusPublished - 2001
Externally publishedYes

ASJC Scopus subject areas

  • Gastroenterology

Keywords

  • Colon carcinoma
  • E-cadherin
  • p53 mutations
  • Transfection

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