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1
Genetic variation in PSCA is associated with susceptibility to diffuse-type gastric cancer

Sakamoto, Hiromi,Yoshimura, Kimio,Saeki, Norihisa,Katai, Hitoshi,Shimoda, Tadakazu,Matsuno, Yoshihiro,Saito, Daizo,Sugimura, Haruhiko,Tanioka, Fumihiko,Kato, Shunji,Matsukura, Norio,Matsuda, Noriko,Na Nature Pub. Co 2008 Nature genetics Vol.40 No.6
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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 = 1.38–1.89, P = 1.11 × 10−9). The association was far less significant in intestinal-type gastric cancer. We found that PSCA is expressed in differentiating gastric epithelial cells, has a cell-proliferation inhibition activity in vitro and is frequently silenced in gastric cancer. Substitution of the C allele with the risk allele T at a SNP in the first exon (rs2294008, which has r2 = 0.995, D′ = 0.999 with rs2976392) reduces transcriptional activity of an upstream fragment of the gene. The same risk allele was also significantly associated with diffuse-type gastric cancer in 457 cases and 390 controls in Korea (allele-specific OR = 1.90, 95% CI = 1.56–2.33, P = 8.01 × 10−11). The polymorphism of the PSCA gene, which is possibly involved in regulating gastric epithelial-cell proliferation, influences susceptibility to diffuse-type gastric cancer.
2
Prostate stem cell antigen gene is expressed in islets of pancreas

Hiroe Ono,Kazuyoshi Yanagihara,Hiromi Sakamoto,Teruhiko Yoshida,Norihisa Saeki 대한해부학회 2012 Anatomy & Cell Biology Vol.45 No.3
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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. Previously it was reported that PSCA is not expressed in the normal pancreas but aberrantly expressed in pancreatic cancer. In this present study, we identified PSCA expression in islets of the pancreas by immunohistochemistry, which was co-localized with four islet-cell markers: insulin, glucagon, somatostatin and pancreatic polypeptide. In our investigation of the transcription start site of PSCA, we found a non-coding splicing variant of PSCA as well as authentic PSCA transcripts in mRNA samples from a normal pancreas. Both the transcripts were also identified in several pancreatic cancer cell lines. We previously reported that PSCA expression is correlated to the methylation status of the enhancer region in gastric and gallbladder cancer cell lines but not in pancreatic cancer cell lines, suggesting that PSCA expression is regulated in a different mode in pancreatic cancer from that in gastric and gallbladder cancers.