title: Expression of Indian hedgehog is negatively correlated with APC gene mutation in colorectal tumors.
abstract: The regulatory mechanism of Indian hedgehog (IHH) in colorectal carcinogenesis has not been elucidated. In the current study, the expression of IHH were investigated in 7 digestive tract cancer cell lines, and in 10 normal colorectal mucosas (NCs), 30 hyperplastic polyps (HPs), 35 colorectal adenomas (ADs), and 40 colorectal adenocarcinomas (CAs) by semi-quantitative RT-PCR and immunohistochemical staining. Moreover, the mutational status of adenomatous polyposis coli (APC) and β-catenin in these tumors were analyzed by direct sequencing. IHH mRNA was lost in the 4 colon cancer cell lines harboring APC mutation. IHH mRNA was significantly decreased in CAs (0.17 ± 0.22), compared with that in ADs (0.38 ± 0.35) and HPs (0.56 ± 0.38, P < 0.05). IHH protein was expressed at a very low level or absent in both ADs (7.51 ± 11.92) and CAs (5.15 ± 9.21) in comparison to that in HPs (19.47 ± 17.91) and NCs (42.40 ± 13.67, P < 0.05). Moreover, APC mutations were negatively correlated with IHH mRNA expression (Spearman's R = -0.636, P < 0.01) and IHH protein expression (Spearman's R = -0.426, P < 0.01). In conclusion, down-regulation of IHH expression might be an early event during the carcinogenesis of colorectal cancer. The activation of Wnt signaling by APC mutation might contribute to the down-regulation or loss of IHH expression in colorectal tumors.
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Luzhou Medical College Sichuan 646000, China.
authors.forename: Xiangsheng
authors.initials: X
authors.lastname: Fu
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Luzhou Medical College Sichuan 646000, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Luzhou Medical College Sichuan 646000, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Luzhou Medical College Sichuan 646000, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Luzhou Medical College Sichuan 646000, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Luzhou Medical College Sichuan 646000, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Luzhou Medical College Sichuan 646000, China.
authors.forename: Chuankang
authors.initials: C
authors.lastname: Tang
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Luzhou Medical College Sichuan 646000, China.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Luzhou Medical College Sichuan 646000, China.
authors.forename: Xian
authors.initials: X
authors.lastname: Zhou
keywords: APC mutation; Indian hedgehog; Wnt signaling pathway; colorectal cancer