Increased Expression of Annexin A1 Is Correlated with K-Ras Mutation in Colorectal Cancer

Increased Expression of Annexin A1 Is Correlated with K-Ras Mutation in Colorectal Cancer

NING SU,¹ XIN-YUN XU,¹ HAN CHEN,¹ WEN-CHAO GAO,¹ CAN-PING RUAN,¹ QIANG WANG¹ and YAN-PING SUN¹

¹Department of General Surgery, Shanghai Chang Zheng Hospital, Second Military Medical University, Shanghai, P.R. China

The activation of K-ras gene and expression of annexin A1 play an important role in colorectal tumorigenesis. We initiated this study to analyze the possible relationship between the annexin A1 expression and the K-ras mutation status in colorectal cancer. K-ras mutations are present in one fourth to one half of colorectal cancers. Annexin A1, a 37-kDa calcium- and phospholipid-binding protein, is over-expressed in colorectal cancers and may be involved in invasive tumor growth and metastasis. Here, we examined twenty paired specimens of colorectal cancer and adjacent normal tissues for K-ras mutations and annexin A1 expression. Sequencing analysis of codons 12 and 13 of K-ras revealed the presence of K-ras mutations in six colorectal cancer tissue specimens (30%). RT-PCR and immunoblotting studies further found that the expression levels of annexin A1 mRNA and protein were increased (2.9-fold and 1.7-fold, respectively) in colorectal cancers harboring K-ras codon 12 or codon 13 mutation compared with adjacent normal tissues (P < 0.05). In colorectal cancer tissues with wild-type K-ras, 12 (85.7%) specimens showed reduced expression of annexin A1 (0.48-fold and 0.81-fold, respectively). No significant association was found between K-ras mutations or annexin A1 over-expression and demographic or other clinicopathological parameters such as gender, differentiation or metastasis. However, a significant and positive correlation was identified between K-ras mutations and annexin A1 over-expression. Our findings indicate that annexin A1 could be implicated in colorectal cancer development and progression and could be of potential use as a predictive marker for guiding targeted therapy for colorectal cancer.

keywords —— colorectal cancer; annexin A1; K-ras; gene mutation; gene expression

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Tohoku J. Exp. Med., 2010, 222, 243-250

Correspondence: Yan-Ping Sun, Department of General Surgery, Shanghai Chang Zheng Hospital, Second Military Medical University, 415 Feng Yang Road, Shanghai, P.R. China.

e-mail: sunyanping2003@yahoo.com