Sonic hedgehog regulates gastric gland morphogenesis in man and mouse

Brink, Gijs R. van den; Hardwick, James C.H.; Peppelenbosch, Maikel P.; Deventer, S. J. H. Van; Tytgat, G. N. J.; Brink, Menno A.; Kate, Fiebo J. ten

doi:10.1053/gast.2001.26261

Cited by 231 publications

(198 citation statements)

References 44 publications

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“…To determine whether blocking or stimulating the Hh signaling pathway would affect the induction of the target proteins ISL-1, BMP-2 and HNF3-␤, 11 Western blot analysis was carried out with the specific antibodies after the addition of 25 M cyclopamine, Hh-Ag 1.2 or Hh-Ag 1.3. This analysis revealed that there were no significant changes in the expression of these target proteins in the analyzed pancreatic cancer cells (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…9 When Hhs bind to Ptc, Smo is released from the inhibitory effect exerted by Ptc. This leads to the activation and translocation of Gli transcriptional factors, which in turn promote the transcription of target genes like Ptc, bone morphogenic protein (BMP-2), hepatic nuclear factor3-␤ (HNF3-␤), islet-1 (ISL-1) 11 and others. The intracellular events that carry the Hh signaling from Smo via the translocation of Gli into the nucleus are unclear.…”

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confidence: 99%

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Indian hedgehog signaling pathway: Expression and regulation in pancreatic cancer

Kayed

Kleeff

Keleg

et al. 2004

Intl Journal of Cancer

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Indian hedgehog signaling pathway: Expression and regulation in pancreatic cancer

Kayed

Kleeff

Keleg

et al. 2004

Intl Journal of Cancer

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“…Sonic hedgehog (SHH), a member of the family of Hedgehog proteins known to exert important regulatory functions in patterning and growth in a large number of tissues during embryogenesis, might be one of the secreted signals lost during progression to atrophy. Immunohistochemical studies in both mice and humans indicate that SHH is expressed by parietal cells (23), and patients with atrophic gastritis exhibit lower levels of SHH immunostaining (24). Importantly, SHH-deficient mice develop a metaplasia of the stomach (25).…”

Section: Atrophic Gastritis and Gastric Cancermentioning

confidence: 99%

Inflammation, atrophy, and gastric cancer

Fox

Wang²

2007

J. Clin. Invest.

691

626

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The association between chronic inflammation and cancer is now well established. This association has recently received renewed interest with the recognition that microbial pathogens can be responsible for the chronic inflammation observed in many cancers, particularly those originating in the gastrointestinal system. A prime example is Helicobacter pylori, which infects 50% of the world's population and is now known to be responsible for inducing chronic gastric inflammation that progresses to atrophy, metaplasia, dysplasia, and gastric cancer. This Review provides an overview of recent progress in elucidating the bacterial properties responsible for colonization of the stomach, persistence in the stomach, and triggering of inflammation, as well as the host factors that have a role in determining whether gastritis progresses to gastric cancer. We also discuss how the increased understanding of the relationship between inflammation and gastric cancer still leaves many questions unanswered regarding recommendations for prevention and treatment.

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“…4 Recent studies demonstrate that Shh is involved in the development of gastric gland and gastric epithelial differentiation in adults. 5 Mutational activation of the Hh signaling pathway, either sporadic or in Gorlin's syndrome, is associated with tumorigenesis in a small subset of tissues, predominantly skin, cerebellum, and skeletal muscle. 6,7 Gorlin's syndrome induced by a heterozygous mutation affecting the Patched gene, receptor for Shh, and is associated with various cancers, including basal cell carcinoma, medulloblastoma, and rhabdomyosarcoma.…”

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confidence: 99%

Increased expression of sonic hedgehog and altered methylation of its promoter region in gastric cancer and its related lesions

et al. 2006

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The hedgehog (Hh) signaling pathway plays an important role in foregut development, and its activity is increased in various tumors, including those of the digestive tract. Our objective in the present study was to determine the pattern and extent of Sonic hedgehog (Shh) expression in gastric cancer and related lesions as well as the methylation status of its promoter region, in an attempt to clarify the regulatory mechanism of Shh expression. A total of 237 gastric cancers and related lesions (89 carcinomas, 22 high-grade dysplasia, 21 lowgrade dysplasia, 47 intestinal metaplasia, 38 chronic gastritis, and 20 normal epithelia) were subjected to immunohistochemical analysis with the Shh monoclonal antibody. The methylation status of Shh was determined by methylation-specific PCR (MS PCR), involving bisulfate treatment of DNA from 150 tissues followed by amplification using specific primer pairs designed by our group. Shh was completely absent in the upper part of normal gastric epithelia (gastric pit cells), and no significant differences were observed among the lower parts of normal epithelia, chronic gastritis, and intestinal metaplasia. However, Shh expression was significantly elevated in neoplastic lesions, such as carcinoma and high low-grade dysplasia, compared to nonneoplastic lesions. In carcinomas, Shh expression was associated with clinical stage, direct tumor invasion, and differentiation of tumor cells. Methylation of the Shh promoter region was frequent in normal gastric pit cells (11/18, 61.1%), but very rare in gastritis (0/18), intestinal metaplasia (0/19), dysplasia (0/10), and carcinoma (1/63, 1.6%), and correlated significantly with expression (Po0.001). Our results suggested that the increased and constitutive Shh expression is implicated in gastric carcinogenesis, and that promoter methylation may be an important regulatory mechanism of Shh expression.

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Sonic hedgehog regulates gastric gland morphogenesis in man and mouse

Cited by 231 publications

References 44 publications

Indian hedgehog signaling pathway: Expression and regulation in pancreatic cancer

Indian hedgehog signaling pathway: Expression and regulation in pancreatic cancer

Inflammation, atrophy, and gastric cancer

Increased expression of sonic hedgehog and altered methylation of its promoter region in gastric cancer and its related lesions

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