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Identification of the Transforming Activity of Indian Hedgehog by Retroviral Expression Screening

Abstract

To identify novel cancer-promoting genes in biliary tract cancer (BTC), we constructed a retroviral cDNA expression library from a clinical specimen of BTC with anomalous pancreaticobiliary duct junction (APBDJ), and used the library for a focus formation assay with 3T3 fibroblasts. One of the cDNAs rescued from transformed foci was found to encode Indian hedgehog homolog (IHH). The oncogenic potential of IHH was confirmed both in vitro with the focus formation assay and in vivo with a tumorigenicity assay in nude mice. The isolated IHH cDNA had no sequence alterations, suggesting that upregulation of IHH expression may contribute to malignant transformation. Quantitation of IHH mRNA among clinical specimens has revealed that the expression level of IHH in BTC with APBDJ is higher than that in BTC without APBDJ and than in non-cancerous biliary tissues. Our data thus implicate a direct role of IHH in the carcinogenesis of BTC with APBDJ.

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References
1.
Hasumi A, Matsui H, Sugioka A, Uyama I, Komori Y, Fujita J . Precancerous conditions of biliary tract cancer in patients with pancreaticobiliary maljunction: reappraisal of nationwide survey in Japan. J Hepatobiliary Pancreat Surg. 2001; 7(6):551-5. DOI: 10.1007/s005340070003. View

2.
Reifenberger J, Wolter M, Weber R, Megahed M, Ruzicka T, Lichter P . Missense mutations in SMOH in sporadic basal cell carcinomas of the skin and primitive neuroectodermal tumors of the central nervous system. Cancer Res. 1998; 58(9):1798-803. View

3.
Beachy P, Karhadkar S, Berman D . Tissue repair and stem cell renewal in carcinogenesis. Nature. 2004; 432(7015):324-31. DOI: 10.1038/nature03100. View

4.
Hui A, Li X, Shi Y, Takayama T, Torzilli G, Makuuchi M . Cyclin D1 overexpression is a critical event in gallbladder carcinogenesis and independently predicts decreased survival for patients with gallbladder carcinoma. Clin Cancer Res. 2000; 6(11):4272-7. View

5.
Nusslein-Volhard C, Wieschaus E . Mutations affecting segment number and polarity in Drosophila. Nature. 1980; 287(5785):795-801. DOI: 10.1038/287795a0. View