Prostate stem cell antigen, a presumable organ‐dependent tumor suppressor gene, is down‐regulated in gallbladder carcinogenesis

Ono, Hiroe; Hiraoka, Nobuyoshi; Lee, Yeon Su; Woo, Sang Myung; Lee, Woojin; Choi, Il Ju; Saito, Akira; Yanagihara, Kazuyoshi; Kanai, Yae; Ohnami, Sumiko; Chiwaki, Fumiko; Sasaki, Hiroki; Sanada, Hiromi; Yoshida, Teruhiko; Saeki, Norihisa

doi:10.1002/gcc.20928

Cited by 38 publications

(71 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…(35) The GBC cells introduced with PSCA cDNA showed lower in vitro and in vivo growth than controls, and their invasion ability assayed with a Matrigel chamber was also attenuated. (35) PSCA is expressed homogenously in normal gallbladder epithelium, which is characterized by a mono-layer of columner cells and functions by absorbing water and electrolytes. It is possible that PSCA has a role in cell-division control and/or other activities such as active transport of molecules in gallbladder epithelium.…”

Section: à6mentioning

confidence: 94%

“…(37) The discrepancy between the in vitro reporter assay and the in vivo expression data further suggests a complexity of the PSCA regulation, which might be influenced by tissue-specific transcriptional factors and DNA methylation, as shown in gastric and gallbladder cancer cell lines. (35) In contrast, a recent study reported that the C allele of rs2294008 in PSCA was associated with an increased risk of duodenal ulcer (DU; odds ratio = 1.84; P = 3.92 9 10 À33 in a recessive model). (38) Moreover, the results of functional analyses showed that the C allele changes the subcellular localization of PSCA protein from the cell surface to the cytoplasm and also reduced the protein's stability.…”

Section: à6mentioning

confidence: 94%

“…(12,34) Recently, we have reported that the gene is also downregulated in gallbladder cancer. (35) Intriguingly, both gallbladder cancer and IGC develop in a similar sequence of chronic inflammation, intestinal metaplasia, dysplasia and cancer. Moreover, PSCA is downregulated in intestinal metaplasia in both gallbladder and gastric epithelia.…”

Section: à6mentioning

confidence: 99%

“…Moreover, PSCA is downregulated in intestinal metaplasia in both gallbladder and gastric epithelia. (12,35) There could be other cancers in which PSCA is silenced during carcinogenesis.…”

Section: à6mentioning

confidence: 99%

“…The T allele associated with the risk for GC has a negative effect on the promoter activity in gastric, urinary bladder and gallbladder cancer cell lines. (12,22,35) Therefore, it is anticipated that people possessing the T allele have a lower amount of PSCA protein in the organs than those possessing the C allele. However, recent microarray transcriptome analyses showed that normal and malignant urinary bladder tissues from people with the T allele contained more PSCA transcripts than those from people with the C allele.…”

Section: à6mentioning

confidence: 99%

See 4 more Smart Citations

Genetic factors related to gastric cancer susceptibility identified using a genome‐wide association study

et al. 2012

Self Cite

View full text Add to dashboard Cite

Gastric cancer (GC) is one of the major malignant diseases worldwide, especially in Asia, where Japan and Korea have the highest incidence in the world. Gastric cancer is classified into intestinal and diffuse types. While the former is almost absolutely caused by Helicobacter pylori infection as the initial insult, the latter seems to include cases in which the role of infection is limited, if any, and a contribution of genetic factors is anticipated. Previously, we performed a genome-wide association study (GWAS) on diffusetype GC by using single nucleotide polymorphisms (SNP) catalogued for Japanese population (JSNP), and identified a prostate stem cell antigen (PSCA) gene encoding a glycosylphosphatidylinositol-anchored cell surface antigen as a GC susceptibility gene. From the second candidate locus identified using the GWAS, 1q22, we found the Mucin 1 (MUC1) gene encoding a cell membranebound mucin protein as another gene related to diffuse-type GC. A two-allele analysis based on risk genotypes of the two genes revealed approximately 95% of Japanese population have at least one of the two risk genotypes, and approximately 56% of the population have both risk genotypes. The two-SNP genotype might offer ample room to further stratify a high GC risk subpopulation in Japan and Asia by adding another genetic and/or non-genetic factor. Recently, a GWAS on the Chinese population disclosed an additional three GC susceptibility loci: 3q13.31, 5p13.1 and 10q23. (Cancer Sci 2013; 104: 1-8) G astric cancer (GC) is one of the major malignant diseases and the second causal of cancer death worldwide.(1) It is usually classified into two types, intestinal and diffuse, a classification which was originally based on histological observation but is recently thought to reflect its pathogenesis.(2) The majority of intestinal-type GC (IGC) arises in the sequence of inflammatory change of the gastric epithelium resulting from bacterial infection; Helicobacter pylori (HP) infectionchronic inflammation -intestinal metaplasia -dysplasia -adenocarcinoma. In contrast, de novo diffuse-type GC (DGC) is thought to emerge in a histologically almost normal epithelium as a consequence of some genetic change that occurred in gastric stem cells and/or epithelial precursor cells, although some cases with DGC might represent dedifferentiated stages of IGC, and a contribution of HP is also suggested.(3) In other words, it is apparent that the pathogenesis of IGC is initiated by HP infection, a class I carcinogen acknowledged by WHO, and therefore IGC is essentially a preventable disease by eradicating HP infection. However, DGC might develop earlier in life than IGC, (4) and no definite DGC-specific environmental risk factor has been established. Therefore, so far we have neither solid strategy nor promising theory to envision a consistent diminution of the incidence of DGC.The incidence of GC has strong geographical and ethnical characteristics. For example, it is one of the rare cancers in North America and Europe, while its incidence is s...

show abstract

Section: à6mentioning

confidence: 94%

Section: à6mentioning

confidence: 94%

Section: à6mentioning

confidence: 99%

“…Moreover, PSCA is downregulated in intestinal metaplasia in both gallbladder and gastric epithelia. (12,35) There could be other cancers in which PSCA is silenced during carcinogenesis.…”

Section: à6mentioning

confidence: 99%

Section: à6mentioning

confidence: 99%

See 3 more Smart Citations

Genetic factors related to gastric cancer susceptibility identified using a genome‐wide association study

et al. 2012

Self Cite

View full text Add to dashboard Cite

show abstract

Association ofPSCArs2294008 gene variants with poor prognosis and increased susceptibility to gastric cancer and decreased risk of duodenal ulcer disease

et al. 2015

View full text Add to dashboard Cite

Two recent genome-wide association studies in Asians have reported the association between the PSCA (prostate stem cell antigen) rs2294008C>T gene polymorphism and two Helicobacter pylori infection-related diseases such as gastric cancer (GC) and duodenal ulcer (DU). Since rs2294008 allele frequencies differ notably among ethnicities, we aimed to assess the role of rs2294008 on the susceptibility to GC and DU in a Caucasian population in Spain. Moreover, the relevance of rs2294008 on GC prognosis was evaluated. Genomic DNA from 603 Spanish patients with primary GC, 139 with DU and 675 healthy controls was typed for the PSCA rs2294008C>T polymorphism by PCR-TaqMan assays. H. pylori infection [odds ratio (OR): 8.27; 95% confidence interval (CI): 3.45-15.33] and nonsteroidal anti-inflammatory drugs (OR: 6.54; 95% CI: 3.19-12.43) were identified as independent risk factors for DU whereas the rs2294008T allele was associated with reduced risk of developing the disease (OR: 0.52; 95% CI: 0.33-0.82). Infection with CagA strains (OR: 2.10; 95% CI: 1.63-2.34), smoking (OR: 1.93; 95% CI: 1.54-2.61), family history of GC (OR: 2.83; 95% CI: 2.01-3.83), and the rs2294008T allele (OR: 1.46; 95% CI: 1.07-1.99) were associated with increased risk of GC. Interestingly, the association with the rs2294008T allele was restricted to noncardia GC (OR: 1.43; 95% CI: 1.12-1.82), particularly of the diffuse histotype (OR: 1.59; 95% CI: 1.16-1.92). Finally, Cox regression analysis identified the rs2294008T variant as a prognosis factor associated with worse overall survival in patients with diffuse-type GC (hazard ratio: 1.85; 95% CI: 1.12-3.06). From these results we conclude that the PSCA rs2294008 polymorphism is involved in the susceptibility to GC and DU, as well as in the prognosis of the diffuse-type of GC in Caucasians.

show abstract

PSCA promotes prostate cancer proliferation and cell‐cycle progression by up‐regulating c‐Myc

Liu

et al. 2017

The Prostate

View full text Add to dashboard Cite

show abstract

Prostate stem cell antigen, a presumable organ‐dependent tumor suppressor gene, is down‐regulated in gallbladder carcinogenesis

Cited by 38 publications

References 30 publications

Genetic factors related to gastric cancer susceptibility identified using a genome‐wide association study

Genetic factors related to gastric cancer susceptibility identified using a genome‐wide association study

Association ofPSCArs2294008 gene variants with poor prognosis and increased susceptibility to gastric cancer and decreased risk of duodenal ulcer disease

PSCA promotes prostate cancer proliferation and cell‐cycle progression by up‐regulating c‐Myc

Contact Info

Product

Resources

About