CETN1 is a cancer testis antigen with expression in prostate and pancreatic cancers

Biomarker Research

John J Kim⁵  Krithika Rajagopalan⁴  Basil Hussain²  Brenten H Williams³  Prakash Kulkarni³  Steven M Mooney¹ 

[1] Department of Urology and Oncology, James Buchanan Brady Urological Institute, 600 N. Wolfe St. 129B Marburg, Baltimore, MD, 21287, USA

[2] Department of Molecular Biology and Genetics, The Johns Hopkins University, School of Medicine, Baltimore, MD, 21287, USA

[3] Department of Urology, James Buchanan Brady Urological Institute, The Johns Hopkins University, School of Medicine, Baltimore, MD, 21287, USA

[4] Department of Biological Sciences, Columbia University, New York, NY, 10027, USA

[5] Department of Biomedical Engineering, Whiting School of Engineering, The Johns Hopkins University, School of Medicine, Baltimore, MD, 21287, USA

关键词: CTA;    Pancreas;    Prostate;    Cancer;    CETN3;    CETN2;    CETN1;    CDC31;    Centrin;    Testis;   

Others  :  791948
DOI  :  10.1186/2050-7771-1-22

 received in 2013-03-24, accepted in 2013-06-03,  发布年份 2013

【 摘 要 】

Background

The Cancer Testis Antigens (CTAs) are a group of genes that are highly expressed in the normal testis and several types of cancer. Due to their restricted expression in normal adult tissues, CTAs have been attractive targets for immunotherapy and biomarker development. In this work, we discovered that Centrin 1 (CETN1) which is found in the centrosome of all eukaryotes, may be a member of this group and is highly expressed in prostate and pancreatic cancer. Three members of the centrin family of calcium binding proteins (CETN) are localized to the centrosome in all eukaryotes with CDC31 being the sole yeast homolog. CETN1 is a retrogene that probably arose from a retrotransposition of CETN2, an X-linked gene. A previous mouse study shows that CETN1 is expressed solely in the testis, while CETN2 is expressed in all organs.

Results

In this work, we show that CETN1 is a new member of the growing group of CTAs. Through the mining of publicly available microarray data, we discovered that human CETN1 expression but not CETN2 or CETN3 is restricted to the testis. In fact, CETN1 is actually down-regulated in testicular malignancies compared to normal testis. Using q-PCR, CETN1 expression is shown to be highly up-regulated in cancer of the prostate and in pancreatic xenografts. Unexpectedly however, CETN1 expression was virtually absent in various cell lines until they were treated with the DNA demethylation agent 5’AZA-2’Deoxycytidine (AZA) but showed no increased expression upon incubation with Histone deacetylase inhibitor Trichostatin-A (TSA) alone. Additionally, like most CTAs, CETN1 appears to be an intrinsically disordered protein which implies that it may occupy a hub position in key protein interaction networks in cancer. Neither CETN1 nor CETN2 could compensate for loss of CDC31 expression in yeast which is analogous to published data for CETN3.

Conclusions

This work suggests that CETN1 is a novel CTA with expression in cancer of the prostate and pancreas. In cell lines, the expression is probably regulated by promoter methylation, while the method of regulation in normal adult tissues remains unknown.

【 授权许可】

   
2013 Kim et al.; licensee BioMed Central Ltd.

【 图 表 】

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