Frequent activation of the hedgehog pathway in advanced gastric adenocarcinomas

Xiaoli Ma, Kai Chen, Shuhong Huang, Xiaoli Zhang, Patrick A. Adegboyega, B. Mark Evers, Hongwei Zhang, Jingwu Xie

Research output: Contribution to journalArticle

172 Citations (Scopus)

Abstract

The hedgehog pathway plays a critical role in the development of the foregut. Recent studies indicate that the hedgehog pathway activation occurs in the stomach and other gastrointestinal cancers. However, the association of hedgehog pathway activation with tumor stage, differentiation and tumor subtype is not well documented. Here, we report our findings that the elevated expression of hedgehog target genes human patched gene 1 (PTCH1) or Gli1 occurs in 63 of the 99 primary gastric cancers. Activation of the hedgehog pathway is associated with poorly differentiated and more aggressive tumors. The sonic hedgehog (Shh) transcript is localized to the cancer tissue, whereas expression of Gli1 and PTCH1 is observed both in the cancer and in the surrounding stroma. Treatment of gastric cancer cells with KAAD-cyclopamine, a hedgehog signaling inhibitor, decreases expression of Gli1 and PTCH1, resulting in cell growth inhibition and apoptosis. Overexpression of Gli1 under the control of the cytomegalovirus (CMV) promoter renders these cells resistant to cyclopamine-induced apoptosis. Thus, our analysis of in vivo tissues indicates that the hedgehog pathway is frequently activated in advanced gastric adenocarcinomas; our in vitro studies suggest that hedgehog signaling contributes to gastric cancer cell growth. These data predict that targeted inhibition of the hedgehog pathway may be effective in the prevention and treatment of advanced gastric adenocarcinomas.

Original languageEnglish (US)
Pages (from-to)1698-1705
Number of pages8
JournalCarcinogenesis
Volume26
Issue number10
DOIs
StatePublished - Oct 2005
Externally publishedYes

Fingerprint

Stomach
Adenocarcinoma
Stomach Neoplasms
Neoplasms
Genes
Apoptosis
Gastrointestinal Neoplasms
Growth
Cytomegalovirus

ASJC Scopus subject areas

  • Cancer Research

Cite this

Ma, X., Chen, K., Huang, S., Zhang, X., Adegboyega, P. A., Evers, B. M., ... Xie, J. (2005). Frequent activation of the hedgehog pathway in advanced gastric adenocarcinomas. Carcinogenesis, 26(10), 1698-1705. https://doi.org/10.1093/carcin/bgi130

Frequent activation of the hedgehog pathway in advanced gastric adenocarcinomas. / Ma, Xiaoli; Chen, Kai; Huang, Shuhong; Zhang, Xiaoli; Adegboyega, Patrick A.; Evers, B. Mark; Zhang, Hongwei; Xie, Jingwu.

In: Carcinogenesis, Vol. 26, No. 10, 10.2005, p. 1698-1705.

Research output: Contribution to journalArticle

Ma, X, Chen, K, Huang, S, Zhang, X, Adegboyega, PA, Evers, BM, Zhang, H & Xie, J 2005, 'Frequent activation of the hedgehog pathway in advanced gastric adenocarcinomas', Carcinogenesis, vol. 26, no. 10, pp. 1698-1705. https://doi.org/10.1093/carcin/bgi130
Ma X, Chen K, Huang S, Zhang X, Adegboyega PA, Evers BM et al. Frequent activation of the hedgehog pathway in advanced gastric adenocarcinomas. Carcinogenesis. 2005 Oct;26(10):1698-1705. https://doi.org/10.1093/carcin/bgi130
Ma, Xiaoli ; Chen, Kai ; Huang, Shuhong ; Zhang, Xiaoli ; Adegboyega, Patrick A. ; Evers, B. Mark ; Zhang, Hongwei ; Xie, Jingwu. / Frequent activation of the hedgehog pathway in advanced gastric adenocarcinomas. In: Carcinogenesis. 2005 ; Vol. 26, No. 10. pp. 1698-1705.
@article{c7b58024bf3140ccacac80f1dc4442e6,
title = "Frequent activation of the hedgehog pathway in advanced gastric adenocarcinomas",
abstract = "The hedgehog pathway plays a critical role in the development of the foregut. Recent studies indicate that the hedgehog pathway activation occurs in the stomach and other gastrointestinal cancers. However, the association of hedgehog pathway activation with tumor stage, differentiation and tumor subtype is not well documented. Here, we report our findings that the elevated expression of hedgehog target genes human patched gene 1 (PTCH1) or Gli1 occurs in 63 of the 99 primary gastric cancers. Activation of the hedgehog pathway is associated with poorly differentiated and more aggressive tumors. The sonic hedgehog (Shh) transcript is localized to the cancer tissue, whereas expression of Gli1 and PTCH1 is observed both in the cancer and in the surrounding stroma. Treatment of gastric cancer cells with KAAD-cyclopamine, a hedgehog signaling inhibitor, decreases expression of Gli1 and PTCH1, resulting in cell growth inhibition and apoptosis. Overexpression of Gli1 under the control of the cytomegalovirus (CMV) promoter renders these cells resistant to cyclopamine-induced apoptosis. Thus, our analysis of in vivo tissues indicates that the hedgehog pathway is frequently activated in advanced gastric adenocarcinomas; our in vitro studies suggest that hedgehog signaling contributes to gastric cancer cell growth. These data predict that targeted inhibition of the hedgehog pathway may be effective in the prevention and treatment of advanced gastric adenocarcinomas.",
author = "Xiaoli Ma and Kai Chen and Shuhong Huang and Xiaoli Zhang and Adegboyega, {Patrick A.} and Evers, {B. Mark} and Hongwei Zhang and Jingwu Xie",
year = "2005",
month = "10",
doi = "10.1093/carcin/bgi130",
language = "English (US)",
volume = "26",
pages = "1698--1705",
journal = "Carcinogenesis",
issn = "0143-3334",
publisher = "Oxford University Press",
number = "10",

}

TY - JOUR

T1 - Frequent activation of the hedgehog pathway in advanced gastric adenocarcinomas

AU - Ma, Xiaoli

AU - Chen, Kai

AU - Huang, Shuhong

AU - Zhang, Xiaoli

AU - Adegboyega, Patrick A.

AU - Evers, B. Mark

AU - Zhang, Hongwei

AU - Xie, Jingwu

PY - 2005/10

Y1 - 2005/10

N2 - The hedgehog pathway plays a critical role in the development of the foregut. Recent studies indicate that the hedgehog pathway activation occurs in the stomach and other gastrointestinal cancers. However, the association of hedgehog pathway activation with tumor stage, differentiation and tumor subtype is not well documented. Here, we report our findings that the elevated expression of hedgehog target genes human patched gene 1 (PTCH1) or Gli1 occurs in 63 of the 99 primary gastric cancers. Activation of the hedgehog pathway is associated with poorly differentiated and more aggressive tumors. The sonic hedgehog (Shh) transcript is localized to the cancer tissue, whereas expression of Gli1 and PTCH1 is observed both in the cancer and in the surrounding stroma. Treatment of gastric cancer cells with KAAD-cyclopamine, a hedgehog signaling inhibitor, decreases expression of Gli1 and PTCH1, resulting in cell growth inhibition and apoptosis. Overexpression of Gli1 under the control of the cytomegalovirus (CMV) promoter renders these cells resistant to cyclopamine-induced apoptosis. Thus, our analysis of in vivo tissues indicates that the hedgehog pathway is frequently activated in advanced gastric adenocarcinomas; our in vitro studies suggest that hedgehog signaling contributes to gastric cancer cell growth. These data predict that targeted inhibition of the hedgehog pathway may be effective in the prevention and treatment of advanced gastric adenocarcinomas.

AB - The hedgehog pathway plays a critical role in the development of the foregut. Recent studies indicate that the hedgehog pathway activation occurs in the stomach and other gastrointestinal cancers. However, the association of hedgehog pathway activation with tumor stage, differentiation and tumor subtype is not well documented. Here, we report our findings that the elevated expression of hedgehog target genes human patched gene 1 (PTCH1) or Gli1 occurs in 63 of the 99 primary gastric cancers. Activation of the hedgehog pathway is associated with poorly differentiated and more aggressive tumors. The sonic hedgehog (Shh) transcript is localized to the cancer tissue, whereas expression of Gli1 and PTCH1 is observed both in the cancer and in the surrounding stroma. Treatment of gastric cancer cells with KAAD-cyclopamine, a hedgehog signaling inhibitor, decreases expression of Gli1 and PTCH1, resulting in cell growth inhibition and apoptosis. Overexpression of Gli1 under the control of the cytomegalovirus (CMV) promoter renders these cells resistant to cyclopamine-induced apoptosis. Thus, our analysis of in vivo tissues indicates that the hedgehog pathway is frequently activated in advanced gastric adenocarcinomas; our in vitro studies suggest that hedgehog signaling contributes to gastric cancer cell growth. These data predict that targeted inhibition of the hedgehog pathway may be effective in the prevention and treatment of advanced gastric adenocarcinomas.

UR - http://www.scopus.com/inward/record.url?scp=27144541492&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=27144541492&partnerID=8YFLogxK

U2 - 10.1093/carcin/bgi130

DO - 10.1093/carcin/bgi130

M3 - Article

C2 - 15905200

AN - SCOPUS:27144541492

VL - 26

SP - 1698

EP - 1705

JO - Carcinogenesis

JF - Carcinogenesis

SN - 0143-3334

IS - 10

ER -