Indirect Down-regulation of Tumor-suppressive Family MicroRNAs by in Neuroblastoma.

Background/aim: Overall survival for the high-risk group of neuroblastoma (NB) patients still remains at 40-50%, necessitating the establishment of a curable treatment. LIM domain only 1 (LMO1) gene encoding a transcriptional regulator is an NB-susceptibility gene with a tumor-promoting activity. Previously we conducted chromatin immunoprecipitation and DNA sequencing analyses on NB cell lines and identified 3 protein-coding genes regulated by LMO1.

Chromatin Immunoprecipitation and DNA Sequencing Identified a LIMS1/ILK Pathway Regulated by LMO1 in Neuroblastoma.

Background/aim: Overall survival for the high-risk group of neuroblastoma (NB) remains at 40-50%. An integrative genomics study revealed that LIM domain only 1 (LMO1) encoding a transcriptional regulator to be an NB-susceptibility gene with a tumor-promoting activity, that needs to be revealed.

Materials And Methods: We conducted chromatin immunoprecipitation and DNA sequencing analyses and cell proliferation assays on two NB cell lines.

Prostate stem cell antigen is expressed in normal and malignant human brain tissues.

Prostate stem cell antigen (PSCA) is a glycosylphosphatidylinositol (GPI)-anchored cell surface protein and exhibits an organ-dependent expression pattern in cancer. PSCA is upregulated in prostate cancer and downregulated in gastric cancer. PSCA is expressed in a variety of human organs.

A GSDMB enhancer-driven HSV thymidine kinase-expressing vector for controlling occult peritoneal dissemination of gastric cancer cells.

Background: Gastric cancer (GC) is one of the major malignant diseases worldwide, especially in Asia, and Japan and Korea have the highest incidence in the world. Because most of the cases that are refractory to therapies die due to peritoneal dissemination (PD) of the cancer cells, controlling PD is important for patient survival. GSDMB is a member of the gasdermin gene family.

Down-regulation of Immune-related Genes by PSCA in Gallbladder Cancer Cells Implanted into Mice.

Background/aim: In previous work, we found that prostate stem cell antigen (PSCA) gene, encoding a glycosylphosphatidylinositol-anchored protein, is a presumable tumor suppressor in gastric cancer and gallbladder cancer (GBC). The introduction of PSCA cDNA into GBC cell lines significantly suppressed tumorigenecity of cells in mice. The PSCA protein is thought to be involved in some form of intracellular signaling that remains to be elucidated.

rs2294008T, a risk allele for gastric and gallbladder cancers, suppresses the PSCA promoter by recruiting the transcription factor YY1.

Previous genomewide association studies identified prostate stem cell antigen (PSCA) as a gastric cancer (GC) susceptibility gene and showed an association between GC and the T allele of the single nucleotide polymorphism rs2294008 (C/T) in this gene. The protein product of this gene inhibits cell growth, and the T allele significantly suppresses the transcriptional activity of the -3.2 kb PSCA upstream region.

Mucin 1 gene (MUC1) and gastric-cancer susceptibility.

Gastric cancer (GC) is one of the major malignant diseases worldwide, especially in Asia. It is classified into intestinal and diffuse types. While the intestinal-type GC (IGC) is almost certainly caused by Helicobacter pylori (HP) infection, its role in the diffuse-type GC (DGC) appears limited.

Missense allele of a single nucleotide polymorphism rs2294008 attenuated antitumor effects of prostate stem cell antigen in gallbladder cancer cells.

Background: Prostate stem cell antigen (PSCA), an organ-dependent tumor suppressor, is down regulated in gallbladder cancer (GBC). It is anticipated that the missense allele C of the single nucleotide polymorphism (SNP) rs2294008 (T/C) in the translation initiation codon of the gene affects the gene's biological function and has some influence on GBC susceptibility. We examined the biological effect of the C allele on the function of the gene and the relation between the C allele and GBC susceptibility.

Prostate stem cell antigen gene is expressed in islets of pancreas.

Prostate stem cell antigen (PSCA) is a glycosylphosphatidylinositol-anchored cell surface antigen with an organ-dependent expression pattern in cancers; e.g., up-regulated in prostate cancer and down-regulated in gastric cancer.

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

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.

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

Gallbladder cancer (GBC) is relatively rare but has a high mortality rate. One candidate molecule which might be involved in GBC development is prostate stem cell antigen (PSCA), a glycosylphosphatidylinositol-anchored cell surface antigen with a tissue-specific pattern of expression in the epithelium of several organs, such as the prostate, stomach, bladder, and gallbladder. It is up-regulated in a number of cancers including prostate, urinary bladder, and pancreatic cancers, while it is down-regulated in esophageal and gastric cancers, suggesting that PSCA has an oncogenic activity in the former but a tumor suppressor activity in the latter.

Integrative genomics identifies LMO1 as a neuroblastoma oncogene.

Neuroblastoma is a childhood cancer of the sympathetic nervous system that accounts for approximately 10% of all paediatric oncology deaths. To identify genetic risk factors for neuroblastoma, we performed a genome-wide association study (GWAS) on 2,251 patients and 6,097 control subjects of European ancestry from four case series. Here we report a significant association within LIM domain only 1 (LMO1) at 11p15.

A functional single nucleotide polymorphism in mucin 1, at chromosome 1q22, determines susceptibility to diffuse-type gastric cancer.

Background & Aims: Two major types of gastric cancer, intestinal and diffuse, develop through distinct mechanisms; the diffuse type is considered to be more influenced by genetic factors, although the mechanism is unknown. Our previous genome-wide association study associated 3 single nucleotide polymorphisms (SNPs) with diffuse-type gastric cancer (DGC); 1 was a functional SNP (rs2294008) in prostate stem cell antigen (PSCA), but the loci of the other 2 were not investigated.

Methods: We performed high-density mapping to explore a linkage disequilibrium status of the 2 SNPs at chromosome 1q22.

Genome-wide germline analyses on cancer susceptibility and GeMDBJ database: Gastric cancer as an example.

The power of an SNP-based genome-wide association study (GWAS) was first demonstrated in Japan using the JSNP database and is currently a major strategy adopted around the world for a number of common diseases including cancers. The hypothesis-free strategy can lead us to a novel hypothesis for carcinogenesis and may contribute to identifying a high risk group for research and, in the future, practice of personalized prevention. We performed a GWAS on diffuse-type gastric cancer and identified a significant association with SNPs in the PSCA (prostate stem cell antigen) gene.

Prostate stem cell antigen: a Jekyll and Hyde molecule?

Prostate stem cell antigen (PSCA) is a glycosylphosphatidylinositol (GPI)-anchored cell surface protein. Although PSCA is thought to be involved in intracellular signaling, much remains unknown about its physiological function and regulatory mechanism in normal and cancer cells. It is up-regulated in several major cancers including prostate, bladder, and pancreatic cancers.

Genetic variation in the prostate stem cell antigen gene PSCA confers susceptibility to urinary bladder cancer.

We conducted a genome-wide association study on 969 bladder cancer cases and 957 controls from Texas. For fast-track validation, we evaluated 60 SNPs in three additional US populations and validated the top SNP in nine European populations. A missense variant (rs2294008) in the PSCA gene showed consistent association with bladder cancer in US and European populations.

[Genome-wide association study of gastric cancer and GeMDBJ database].

A genome-wide association study on diffuse-type gastric cancer identified the PSCA gene, whose exact function in the gastric epithelium has been unknown. Immunohistochemical analysis revealed that PSCA is expressed in the region in which gastric epithelial stem cells and precursors are considered to reside. Moreover, the PSCA was downregulated in gastric cancer tissues, and its product showed a cell-growth inhibition activity in vitro.

Distinctive expression and function of four GSDM family genes (GSDMA-D) in normal and malignant upper gastrointestinal epithelium.

Gasdermin (GSDM or GSDMA), expressed in the upper gastrointestinal tract but frequently silenced in gastric cancers (GCs), regulates apoptosis of the gastric epithelium. It has three human homologs, GSDMB, GSDMC, and GSDMD (GSDM family) and they are considered to be involved in the regulation of epithelial apoptosis but not yet known. We investigated the expression pattern of the family genes in the upper gastrointestinal epithelium and cancers.

Genetic variation in PSCA is associated with susceptibility to diffuse-type gastric cancer.

Gastric cancer is classified into intestinal and diffuse types, the latter including a highly malignant form, linitis plastica. A two-stage genome-wide association study (stage 1: 85,576 SNPs on 188 cases and 752 references; stage 2: 2,753 SNPs on 749 cases and 750 controls) in Japan identified a significant association between an intronic SNP (rs2976392) in PSCA (prostate stem cell antigen) and diffuse-type gastric cancer (allele-specific odds ratio (OR) = 1.62, 95% CI = 1.

Expression status of RUNX1/AML1 in normal gastric epithelium and its mutational analysis in microdissected gastric cancer cells.

Although Runt-related transcription factors RUNXs (RUNX1-3) have a high similarity in their structure, only RUNX3 is known to be involved in gastric carcinogenesis. First, we examined mRNA expression of these three RUNX genes in the gastric mucosa, and, finding only RUNX2 was not expressed there, we further investigated RUNX1 and RUNX3 expression in three regions including the pit, isthmus/neck, and gland regions of the human normal stomach and whether RUNX1 is involved in gastric carcinogenesis. The mRNA expression of RUNX1 and RUNX3 was examined by use of the three regions isolated by laser-captured microdissection (LCM) and by use of primary gastric cancer tissues.

Hedgehog signal activation in gastric pit cell and in diffuse-type gastric cancer.

Background & Aims: Sonic hedgehog (SHH) and Indian hedgehog (IHH) have cell-specific actions in some organs. Only SHH has been shown to regulate parietal cell differentiation. This study examined whether SHH, 2 other ligands IHH and Desert hedgehog, and receptors or downstream targets are expressed in normal gastric epithelium or in intestinal and diffuse-type gastric cancers.

Expression profiling in hepatocellular carcinoma with intrahepatic metastasis: identification of high-mobility group I(Y) protein as a molecular marker of hepatocellular carcinoma metastasis.

Hepatocellular carcinoma (HCC) is one of the most common and aggressive human malignancies. Its high mortality rate is mainly a result of intra-hepatic metastases. To investigate the detailed genetic mechanisms in cancer metastasis, we compared the expression profiles of 20 HCCs with intrahepatic metastasis and 10 HCCs without intrahepatic metastasis using an oligonucleotide array.