Differential expression of apoptotic genes PDIA3 and MAP3K5 distinguishes between low- and high-risk prostate cancer

German Cancer Research Center, Division of Molecular Genome Analysis, Im Neuenheimer Feld 580, D-69120 Heidelberg, Germany.
Molecular Cancer (Impact Factor: 4.26). 12/2009; 8(1):130. DOI: 10.1186/1476-4598-8-130
Source: PubMed

ABSTRACT Despite recent progress in the identification of genetic and molecular alterations in prostate cancer, markers associated with tumor progression are scarce. Therefore precise diagnosis of patients and prognosis of the disease remain difficult. This study investigated novel molecular markers discriminating between low and highly aggressive types of prostate cancer.
Using 52 microdissected cell populations of low- and high-risk prostate tumors, we identified via global cDNA microarrays analysis almost 1200 genes being differentially expressed among these groups. These genes were analyzed by statistical, pathway and gene enrichment methods. Twenty selected candidate genes were verified by quantitative real time PCR and immunohistochemistry. In concordance with the mRNA levels, two genes MAP3K5 and PDIA3 exposed differential protein expression. Functional characterization of PDIA3 revealed a pro-apoptotic role of this gene in PC3 prostate cancer cells.
Our analyses provide deeper insights into the molecular changes occurring during prostate cancer progression. The genes MAP3K5 and PDIA3 are associated with malignant stages of prostate cancer and therefore provide novel potential biomarkers.

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    • "Recently published data connected PDIA3 to the apoptotic process and demonstrated PDIA3 had an antiapoptotic effect in the melanoma cell line A375 after ER stress was induced [33]. PDIA3 possibly plays a role in the malignant transformation of prostate and cervical cancer [34,35]. The expression of this gene is induced during neoplastic transformation possibly leading to redox-dependent modulation of cancer-relevant regulatory factors [36,37]. "
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    ABSTRACT: Purpose To identify differentially expressed proteins in the pterygium compared to healthy conjunctiva using a proteomic analysis. Methods Pterygial and healthy conjunctival tissues were obtained from 24 patients undergoing pterygium excision. Total proteins of the pterygia and healthy conjunctiva were analyzed with one-dimensional electrophoresis, and protein bands of interest were excised and subjected to liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-MS/MS) using Thermo’s Finnigan ProteomeX workstation LTQ linear ion trap MS/MS. Using bioinformatics, differentially expressed proteins were classified, and three proteins closely involved in the response to oxidative stress were selected for further validation. Differential expression of these proteins was confirmed with western blot and immunohistochemistry. Results A web-based gene ontology program, DAVID, was used to classify 230 proteins that were differentially expressed in pterygial tissues. Among these genes, we chose three proteins, aldehyde dehydrogenase, dimeric NADP-preferring (ALDH3A1), protein disulfide-isomerase A3 (PDIA3), and peroxiredoxin-2 (PRDX2), that were significantly upregulated in pterygium and further increased in recurrent pterygium. Immunohistochemistry and western blot analysis confirmed that these three proteins were mainly detected in the basal epithelial layer, and their expression was significantly increased in the pterygium compared to normal conjunctiva. Conclusions This study reported increased expression of ALDH3A1, PDIA3, and PRDX2 in pterygia using a proteomic approach. These proteins are presumed to have a protective role against oxidative stress-induced apoptosis. This result is consistent with the hypothesis that oxidative stress is a significant factor in the pathogenesis of pterygia.
    Molecular vision 08/2014; 20:1192-202. · 1.99 Impact Factor
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    • "Three genes that are associated with activation of apoptosis were increased by heat shock: BOK[53], NGFR[54] and STK4, which activated apoptosis through a p53-dependent mechanism [55]. However, another gene that inhibits apoptosis, SERINC3[56] was increased by heat shock and the pro-apoptotic gene, PDIA3[57], was decreased by heat shock. The possible involvement of the ubiquitin system in clearance of proteins damaged by heat shock, as indicated by the large number of genes regulated by heat shock that bind UBC, may also have implications for apoptosis since ubiquitination plays a role in activation of apoptosis responses [58]. "
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    ABSTRACT: Background While initially sensitive to heat shock, the bovine embryo gains thermal resistance as it progresses through development so that physiological heat shock has little effect on development to the blastocyst stage by Day 5 after insemination. Here, experiments using 3’ tag digital gene expression (3’DGE) and real-time PCR were conducted to determine changes in the transcriptome of morula-stage bovine embryos in response to heat shock (40 degrees C for 8 h) that could be associated with thermotolerance. Results Using 3’DGE, expression of 173 genes were modified by heat shock, with 94 genes upregulated by heat shock and 79 genes downregulated by heat shock. A total of 38 differentially-regulated genes were associated with the ubiquitin protein, UBC. Heat shock increased expression of one heat shock protein gene, HSPB11, and one heat shock protein binding protein, HSPBP1, tended to increase expression of HSPA1A and HSPB1, but did not affect expression of 64 other genes encoding heat shock proteins, heat shock transcription factors or proteins interacting with heat shock proteins. Moreover, heat shock increased expression of five genes associated with oxidative stress (AKR7A2, CBR1, GGH, GSTA4, and MAP2K5), decreased expression of HIF3A, but did not affect expression of 42 other genes related to free radical metabolism. Heat shock also had little effect on genes involved in embryonic development. Effects of heat shock for 2, 4 and 8 h on selected heat shock protein and antioxidant genes were also evaluated by real-time PCR. Heat shock increased steady-state amounts of mRNA for HSPA1A (P<0.05) and tended to increase expression of HSP90AA1 (P<0.07) but had no effect on expression of SOD1 or CAT. Conclusions Changes in the transcriptome of the heat-shocked bovine morula indicate that the embryo is largely resistant to effects of heat shock. As a result, transcription of genes involved in thermal protection is muted and there is little disruption of gene networks involved in embryonic development. It is likely that the increased resistance of morula-stage embryos to heat shock as compared to embryos at earlier stages of development is due in part to developmental acquisition of mechanisms to prevent accumulation of denatured proteins and free radical damage.
    Reproductive Biology and Endocrinology 01/2013; 11(1):3. DOI:10.1186/1477-7827-11-3 · 2.23 Impact Factor
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    • "Type 1 papillary renal tumor 3.4, 4.6 Ooi et al. (2011), Kort et al. (2008) Chromophobe renal tumor −7.9, −4.2, −6.4 Ooi et al. (2011), Kort et al. (2008), Yusenko et al. (2009) Oncocytoma −5.5, −5.6 Kort et al. (2008), Yusenko et al. (2009) Adrenal Adrenocortical carcinoma vs. normal adrenal cortex 5.7 Giordano et al. (2009) Pancreatic cancer Pancreatic cancer vs. matched normal tissue 2.9, 4.2, 5.4 Ishikawa et al. (2005), Pei et al. (2009), Donahue et al. (2012) Prostate cancer Mildly upregulated 1.3, 1.6 Pressinotti et al. (2009), Lapointe et al. (2004) Associated with progression Markert et al. (2011), Taylor et al. (2010) Ovarian cancer Serous ovarian tumors or tumor epithelial cells compared to normal −10 to −54 Shahab et al. (2011), King et al. (2011) AML CRNDE is one of 731 genes whose expression "
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    ABSTRACT: CRNDE is the gene symbol for Colorectal Neoplasia Differentially Expressed (non-protein-coding), a long non-coding RNA (lncRNA) gene that expresses multiple splice variants and displays a very tissue-specific pattern of expression. CRNDE was initially identified as a lncRNA whose expression is highly elevated in colorectal cancer, but it is also upregulated in many other solid tumors and in leukemias. Indeed, CRNDE is the most upregulated lncRNA in gliomas and here, as in other cancers, it is associated with a "stemness" signature. CRNDE is expressed in specific regions within the human and mouse brain; the mouse ortholog is high in induced pluripotent stem cells and increases further during neuronal differentiation. We suggest that CRNDE is a multifunctional lncRNA whose different splice forms provide specific functional scaffolds for regulatory complexes, such as the polycomb repressive complex 2 (PRC2) and CoREST chromatin-modifying complexes, which CRNDE helps pilot to target genes.
    Frontiers in Genetics 11/2012; 3:270. DOI:10.3389/fgene.2012.00270
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