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

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

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

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. However, the precise function of PSCA and the regulatory mechanism for its expression in normal and cancer cells are yet to be determined. In this study, immunohistochemical analyses with a specific antibody revealed that PSCA is down-regulated in non-neoplastic gallbladder lesions such as cholesterolosis, cholecystolithiasis, and cholecystitis (9/17; 53%), and also in adenocarcinoma (40/44; 91%), a common neoplasm in gallbladder. Analyses of the DNA methylation status in the GBC cell lines by bisulfite-Pyrosequencing and a reporter assay for the PSCA promoter activity suggested that the down-regulation is explained, at least partly, by DNA methylation. Moreover, colony formation assay revealed that PSCA has cell-proliferation inhibition activity in the GBC cell lines, which was also observed in vivo. These lines of in vivo and in vitro evidence suggest that PSCA is acting as a tumor suppressor in GBC development.

Original languageEnglish
Pages (from-to)30-41
Number of pages12
JournalGenes Chromosomes and Cancer
Volume51
Issue number1
DOIs
Publication statusPublished - 2012 Jan
Externally publishedYes

Fingerprint

Gallbladder Neoplasms
Gallbladder
Tumor Suppressor Genes
Prostate
Carcinogenesis
Stem Cells
Antigens
DNA Methylation
Prostatic Neoplasms
Cholecystolithiasis
Colony-Forming Units Assay
Cell Line
Neoplasms
Glycosylphosphatidylinositols
Cholecystitis
Surface Antigens
Esophageal Neoplasms
Pancreatic Neoplasms
Urinary Bladder Neoplasms
Stomach Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

Cite this

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, Woo Jin; Choi, Il Ju; Saito, Akira; Yanagihara, Kazuyoshi; Kanai, Yae; Ohnami, Sumiko; Chiwaki, Fumiko; Sasaki, Hiroki; Sakamoto, Hiromi; Yoshida, Teruhiko; Saeki, Norihisa.

In: Genes Chromosomes and Cancer, Vol. 51, No. 1, 01.2012, p. 30-41.

Research output: Contribution to journalArticle

Ono, H, Hiraoka, N, Lee, YS, Woo, SM, Lee, WJ, Choi, IJ, Saito, A, Yanagihara, K, Kanai, Y, Ohnami, S, Chiwaki, F, Sasaki, H, Sakamoto, H, Yoshida, T & Saeki, N 2012, 'Prostate stem cell antigen, a presumable organ-dependent tumor suppressor gene, is down-regulated in gallbladder carcinogenesis', Genes Chromosomes and Cancer, vol. 51, no. 1, pp. 30-41. https://doi.org/10.1002/gcc.20928
Ono, Hiroe ; Hiraoka, Nobuyoshi ; Lee, Yeon Su ; Woo, Sang Myung ; Lee, Woo Jin ; Choi, Il Ju ; Saito, Akira ; Yanagihara, Kazuyoshi ; Kanai, Yae ; Ohnami, Sumiko ; Chiwaki, Fumiko ; Sasaki, Hiroki ; Sakamoto, Hiromi ; Yoshida, Teruhiko ; Saeki, Norihisa. / Prostate stem cell antigen, a presumable organ-dependent tumor suppressor gene, is down-regulated in gallbladder carcinogenesis. In: Genes Chromosomes and Cancer. 2012 ; Vol. 51, No. 1. pp. 30-41.
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AU - Lee, Woo Jin

AU - Choi, Il Ju

AU - Saito, Akira

AU - Yanagihara, Kazuyoshi

AU - Kanai, Yae

AU - Ohnami, Sumiko

AU - Chiwaki, Fumiko

AU - Sasaki, Hiroki

AU - Sakamoto, Hiromi

AU - Yoshida, Teruhiko

AU - Saeki, Norihisa

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AB - 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. However, the precise function of PSCA and the regulatory mechanism for its expression in normal and cancer cells are yet to be determined. In this study, immunohistochemical analyses with a specific antibody revealed that PSCA is down-regulated in non-neoplastic gallbladder lesions such as cholesterolosis, cholecystolithiasis, and cholecystitis (9/17; 53%), and also in adenocarcinoma (40/44; 91%), a common neoplasm in gallbladder. Analyses of the DNA methylation status in the GBC cell lines by bisulfite-Pyrosequencing and a reporter assay for the PSCA promoter activity suggested that the down-regulation is explained, at least partly, by DNA methylation. Moreover, colony formation assay revealed that PSCA has cell-proliferation inhibition activity in the GBC cell lines, which was also observed in vivo. These lines of in vivo and in vitro evidence suggest that PSCA is acting as a tumor suppressor in GBC development.

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