Elevated expression of axin2 and hnkd mRNA provides evidence that Wnt/β-catenin signaling is activated in human colon tumors

被引：300

作者：

Yan, D ^{[1
]}

Wiesmann, M ^{[1
]}

Rohan, M ^{[1
]}

Chan, V ^{[1
]}

Jefferson, AB ^{[1
]}

Guo, LD ^{[1
]}

Sakamoto, D ^{[1
]}

Caothien, RH ^{[1
]}

Fuller, JH ^{[1
]}

Reinhard, C ^{[1
]}

Garcia, PD ^{[1
]}

Randazzo, FM ^{[1
]}

Escobedo, J ^{[1
]}

Fantl, WJ ^{[1
]}

Williams, LT ^{[1
]}

机构：

[1] Chiron Corp, Emeryville, CA 94608 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2001年 / 98卷 / 26期

关键词：

D O I：

10.1073/pnas.261574498

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Genetic studies have identified mutations in key regulators of the Wnt/beta -catenin pathway in a variety of cancers, most frequently in colon cancers. However, whether the pathway is activated in clinical cancer samples is not easily determined, and therefore it is useful to find markers that could be surrogates to show activation of the Wnt/beta -catenin pathway. Gene expression profiles were analyzed in SW620, a colon cancer cell line in which beta -catenin levels are stabilized as a consequence of truncated adenomatous polyposis coli and were compared with profiles of the same cells transfected with antisense oligodeoxynucleotides. Treatment of cells with beta -catenin antisense oligodeoxynucleotides resulted in a decrease in the levels of axin2 and human naked cuticle (hnkd) mRNAs. Interestingly, the proteins encoded by both of these mRNAs are known inhibitors of the beta -catenin pathway. In 30 human cell lines derived from different origins, axin2 and hnkd were expressed only in human colon cancer cell lines that are known to have activating mutations in the Wnt/beta -catenin pathway. Further, levels of both axin2 and hnkd mRNA were also found to be elevated in about 65% of laser microdissected cells from human colon tumors compared with laser microdissected cells of normal morphology from the same patient samples. The increased expression of axin2 and hnkd correlated with truncations in adenomatous polyposis coli in the same patient samples. These results reveal that it is possible to detect activation of a carcinogenic pathway in human cancer samples with specific markers.

引用

页码：14973 / 14978

页数：6

共 26 条

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