Anat Cell Biol.  2012 Sep;45(3):149-154. 10.5115/acb.2012.45.3.149.

Prostate stem cell antigen gene is expressed in islets of pancreas

• Ono H
• Yanagihara K
• Sakamoto H
• Yoshida T
• Saeki N

• KMID: 2046741
• DOI: http://doi.org/10.5115/acb.2012.45.3.149

Abstract

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 diff erent mode in pancreatic cancer from that in gastric and gallbladder cancers.

Keyword

GPI-anchored protein; Islet cells; Pancreatic cancer; Splicing variant; Immunohistochemistry

MeSH Terms

Antigens, Surface
Cell Line
Gallbladder Neoplasms
Glucagon
Immunohistochemistry
Insulin
Islets of Langerhans
Methylation
Pancreas
Pancreatic Neoplasms
Pancreatic Polypeptide
Prostate
Prostatic Neoplasms
RNA, Messenger
Somatostatin
Stem Cells
Stomach Neoplasms
Transcription Initiation Site
Antigens, Surface
Glucagon
Insulin
Pancreatic Polypeptide
RNA, Messenger
Somatostatin

Figure

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  Fig. 1 Prostate stem cell antigen (PSCA) is expressed in the islet of human normal pancreas (immunohistochemistry). (A) Double staining with anti-PSCA (blue) and anti-proliferating cell nuclear (brown) antibodies. The right panel is magnification of the islet shown in the left column. (B) Fluorescent double staining of anti-PSCA antibody (red) and four islet-cell markers (blue), insulin (β cell), glucagon (α cell), somatostatin (δ cell) or pancreatic polypeptide (PP cell). Each series of the image was obtained by focusing on the islet-cell markers.

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  Fig. 2 Two splicing variants of the prostate stem cell antigen (PSCA) transcript are expressed in normal pancreatic, gastric and gallbladder tissues and in cancer cell lines derived from their cancers. (A) Quantitative reverse transcription polymerase chain reaction (RT-PCR) revealed PSCA transcript (variant 1) in human normal pancreas. Colon is negative control as PSCA is not expressed in that organ. (B) Schematic representation of the structure of the two variants. Position in chromosome 8q24 is based on NCBI Build 37.3. (C) Quantitative RT-PCR revealed expression of variants 1 and 2 in the normal tissues and the cancer cell lines, and variant 2 is dominant in the pancreas and pancreatic cancer cell lines.

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  Fig. 3 Bisulfite-pyrosequencing revealed that the DNA methylation status of the prostate stem cell antigen (PSCA) enhancer (B) is not correlated to expression level (A) in the pancreatic cancer cell lines.

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