CSE1L modulates Ras-induced cancer cell invasion: correlation of K-Ras mutation and CSE1L expression in colorectal cancer progression.

Abstract

BACKGROUND:

Ras plays an important role in colorectal cancer progression. CSE1L (chromosome segregation 1-like) gene maps to 20q13, a chromosomal region that correlates with colorectal cancer development. We investigated the association of CSE1L with Ras in colorectal cancer progression.

METHODS:

The effect of CSE1L on metastasis-stimulating activity of Ras was studied in an animal model with tumor cells expressing CSE1L-specific shRNA and v-H-Ras. CSE1L expression was evaluated by the immunohistochemical analysis of 127 surgically resected colorectal tumors. K-Ras mutations were analyzed by direct sequencing.

RESULTS:

CSE1L knockdown reduced Ras-induced metastasis of B16F10 melanoma cells in C57BL/6 mice. v-H-Ras expression altered the cellular trafficking of CSE1L and increased CSE1L secretion. Most colorectal tumors were positive for CSE1L staining (98.4%, 125 of 127). Colorectal tumors with K-Ras mutation or high cytoplasmic CSE1L expression were correlated with T status (depth of tumor penetration; P = .004), stage (P = .004), and lymph node metastasis (P = .019).

CONCLUSIONS:

CSE1L may be a target for treating Ras-associated tumors. Analysis of K-Ras mutation and CSE1L expression may provide valuable clinical and pathological information to aid in the determination of treatment options for colorectal cancer.

• Authors: Ming-Chung Jiang, Chung-Min Yeh, Cheng-Jeng Tai, Hung-Chang Chen, Shu-Hui Lin, Tzu-Cheng Su, Shing-Chuan Shen, Woan-Ruoh Lee, Ching-Fong Liao, Li-Tzu Li, Ching-Hsiao Lee, Ying-Chun Chen, Kun-Tu Yeh, Chun-Chao Chang
• Journal: American journal of surgery (Am J Surg) Vol. 206 Issue 3 Pg. 418-27 (Sep 2013) ISSN: 1879-1883 [Electronic] United States
• PMID: 23806821 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers, Tumor
• Cellular Apoptosis Susceptibility Protein
• Codon

Topics

• Adult
• Aged
• Aged, 80 and over
• Animals
• Biomarkers, Tumor (genetics)
• Biopsy
• Cellular Apoptosis Susceptibility Protein (genetics)
• Codon
• Colorectal Neoplasms (genetics)
• Disease Progression
• Female
• Fluorescent Antibody Technique
• Genes, ras (genetics)
• Genetic Predisposition to Disease
• Humans
• Immunoblotting
• Male
• Mice
• Mice, Inbred C57BL
• Middle Aged
• Mutation
• Neoplasm Metastasis (genetics)