Identification of the transforming activity of Indian hedgehog by retroviral expression screening.
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.
Division of Functional Genomics, Jichi Medical University, Tochigi, Japan.
Hisashi
H
Hatanaka
Shuji
S
Takada
Mamiko
M
Tsukui
Young Lim
YL
Choi
Kentaro
K
Kurashina
Manabu
M
Soda
Yoshihiro
Y
Yamashita
Hidenori
H
Haruta
Toru
T
Hamada
Kiichi
K
Tamada
Yoshinori
Y
Hosoya
Naohiro
N
Sata
Hideo
H
Nagai
Yoshikazu
Y
Yasuda
Kentaro
K
Sugano
Hiroyuki
H
Mano
D016475:3T3 Cells; D000818:Animals; D001652:Bile Ducts / Q000002:abnormalities; D001661:Biliary Tract Neoplasms / Q000209:etiology*; D002471:Cell Transformation, Neoplastic; D053823:Hedgehog Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D010183:Pancreatic Ducts / Q000002:abnormalities; D012190:Retroviridae / Q000235:genetics*
D053823:Hedgehog Proteins