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
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DOI：
10.1620/tjem.222.243
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发表时间：
2010-12-01
影响因子：
2.2
通讯作者：
Sun, Yan-Ping
中科院分区：
文献类型：
--
作者：
Su, Ning;Xu, Xin-Yun;Sun, Yan-Ping
K-ras基因的激活和膜联蛋白A1的表达在结直肠肿瘤的发生发展中起重要作用。本研究旨在分析膜联蛋白A1在结直肠癌中的表达与K-ras基因突变状态之间的可能关系。K-ras基因突变存在于四分之一到一半的结直肠癌中。膜联蛋白A1是一种37 kDa的钙和磷脂结合蛋白，在结直肠癌中高表达，可能参与侵袭性肿瘤的生长和转移。在这里，我们检查了20对结直肠癌和邻近正常组织的K-ras突变和膜联蛋白A1的表达。K-ras基因第12、13密码子序列分析显示，6例(30%)结直肠癌组织中存在K-ras基因突变。RT-PCR和免疫印迹研究进一步发现，K-ras密码子12和密码子13突变的结直肠癌组织中Annexin A1的表达水平分别是癌旁正常组织的2.9倍和1.7倍(P<；0.05)。在含有野生型K-ras的结直肠癌组织中，12例(85.7%)Annexin A1表达降低(分别为0.48倍和0.81倍)。未发现K-ras突变或膜联蛋白A1过度表达与性别、分化或转移等人口学或其他临床病理参数之间的显著相关性。然而，K-ras突变和Annexin A1过表达之间存在显著的正相关。我们的发现表明，Annexin A1可能与结直肠癌的发生和发展有关，并可能作为一种潜在的预测标记物用于指导结直肠癌的靶向治疗。
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.