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

• Published in: The Tohoku Journal of Experimental Medicine Vol. 222; no. 4; pp. 243 - 250
• Main Authors: Su, Ning, Xu, Xin-Yun, Chen, Han, Gao, Wen-Chao, Ruan, Can-Ping, Wang, Qiang, Sun, Yan-Ping
• Format: Journal Article
• Language: English
• Published: Japan Tohoku University Medical Press 01.12.2010
• Subjects: annexin A1; Annexin A1 - genetics; Annexin A1 - metabolism; colorectal cancer; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; Demography; Female; gene expression; Gene Expression Regulation, Neoplastic; gene mutation; Humans; K-ras; Male; Mutation - genetics; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins p21(ras); ras Proteins - genetics; RNA, Messenger - genetics; RNA, Messenger - metabolism
• ISSN: 0040-8727; 1349-3329
• DOI: 10.1620/tjem.222.243

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.