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

Abstract

BackgroundThe 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.ResultsIn 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.ConclusionsThis 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.

RNA sequencing reveals PNN and KCNQ1OT1 as predictive biomarkers of clinical outcome in stage III colorectal cancer patients treated with adjuvant chemotherapy

“…CETN1 (centrin‐1) is a gene associated with cancer testing antigens that has been found upregulated in prostatic and in pancreatic cancers . ANP32C (acidic nuclear phosphoprotein 32 family member C) has been suggested to act as an oncogene and has been found overexpressed in poorly differentiated tumors .…”

The Presence of Androgen Receptor Elements Regulates ZEB1 Expression in the Absence of Androgen Receptor

“…PC3-TxR and DU145-TxR came from cell lines treated with the chemotherapy paclitaxel which causes EMT [Kim et al, 2013]. Likewise, PC3-EMT was induced to a mesenchymal phenotype by incubation with M2 macrophages [Roca et al, 2013].…”

“…Induction of ZEB1 protein has been shown in response to long-term exposure to chemotherapy [Kim et al, 2013], incubation with M2 macrophages [Roca et al, 2013] and hypoxia [Salnikov et al, 2012] highlighting the importance of the tumor microenvironment [Yang et al, 2014]. The exact sequence of events that leads environmental stress to increase ZEB1 expression remains unknown.…”

Centrosomal Abnormalities in Pancreatic Cancer: Molecular Mechanisms and Clinical Implications

“…Factors connected to coordination of the cell cycle play an important role in centrosomal regulation. Any alteration in this process may lead to centrosomal abnormalities and consequently initiate pancreatic cancer (21)(22)(23)(24).…”