Alternative spliced variants of the alpha-methylacyl-CoA racemase gene and their expression in prostate cancer

Mubiru, James N.; Shen-Ong, G L; Valente, Anthony J.; Troyer, Dean A.

doi:10.1016/j.gene.2003.11.009

Cited by 27 publications

(34 citation statements)

References 20 publications

(18 reference statements)

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“…The Institutional Animal Care and Use Committee of the Texas Biomedical Research Institute approved all procedures. Human prostate cDNAs were from cryopreserved human prostate tissues that were collected following radical prostatectomies under an Institutional Review Board approved protocol for the Department of Pathology at the University of Texas Health Science Center, San Antonio, and have been described previously [23].…”

Section: Methodsmentioning

confidence: 99%

Analysis of Prostate-Specific Antigen Transcripts in Chimpanzees, Cynomolgus Monkeys, Baboons, and African Green Monkeys

Mubiru

Yang

Olsen³

et al. 2014

PLoS ONE

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The function of prostate-specific antigen (PSA) is to liquefy the semen coagulum so that the released sperm can fuse with the ovum. Fifteen spliced variants of the PSA gene have been reported in humans, but little is known about alternative splicing in nonhuman primates. Positive selection has been reported in sex- and reproductive-related genes from sea urchins to Drosophila to humans; however, there are few studies of adaptive evolution of the PSA gene. Here, using polymerase chain reaction (PCR) product cloning and sequencing, we study PSA transcript variant heterogeneity in the prostates of chimpanzees (Pan troglodytes), cynomolgus monkeys (Macaca fascicularis), baboons (Papio hamadryas anubis), and African green monkeys (Chlorocebus aethiops). Six PSA variants were identified in the chimpanzee prostate, but only two variants were found in cynomolgus monkeys, baboons, and African green monkeys. In the chimpanzee the full-length transcript is expressed at the same magnitude as the transcripts that retain intron 3. We have found previously unidentified splice variants of the PSA gene, some of which might be linked to disease conditions. Selection on the PSA gene was studied in 11 primate species by computational methods using the sequences reported here for African green monkey, cynomolgus monkey, baboon, and chimpanzee and other sequences available in public databases. A codon-based analysis (dN/dS) of the PSA gene identified potential adaptive evolution at five residue sites (Arg45, Lys70, Gln144, Pro189, and Thr203).

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Section: Methodsmentioning

confidence: 99%

Analysis of Prostate-Specific Antigen Transcripts in Chimpanzees, Cynomolgus Monkeys, Baboons, and African Green Monkeys

Mubiru

Yang

Olsen³

et al. 2014

PLoS ONE

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“…This increase in mass from the original 47 kDa is likely due to the dimerization of full length AMACR, [36] which is reported to be the most abundant IA transcript, with its alternatively spliced variants IB (22 kDa) and IIA (28 kDa). [37] Our assumption is supported by the presence of bands with the same molecular weights in the Western blot analysis of AMACR expression in LNCaP C4-2 cells using a polyclonal AMACR-specific antibody.…”

mentioning

confidence: 64%

New Molecular Markers for Prostate Tumor Imaging: A Study on 2‐Methylene Substituted Fatty Acids as New AMACR Inhibitors

Morgenroth

Urusova

Dinger

et al. 2011

Chemistry A European J

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The development of prostate carcinoma is associated with alterations in fatty acid metabolism. α-Methylacyl-CoA racemase (AMACR) is a peroxisomal and mitochondrial enzyme that catalyses interconversion between the (S)/(R)-isomers of a range of α-methylacyl-CoA thioesters. AMACR is involved in the β-oxidation of the dietary branched-chain fatty acids and bile acid intermediates. It is highly expressed in prostate (more than 95 %), colon (92 %), and breast cancers (44 %) but not in the respective normal or hyperplastic tissues. Thus, targeting of AMACR could be a new strategy for molecular imaging and therapy of prostate and some other cancers. Unlabeled 2-methylenacyl-CoA thioesters (12 a-c) were designed as AMACR binding ligands. The thioesters were tested for their ability to inhibit the AMACR-mediated epimerization of (25R)-THC-CoA and were found to be strong AMACR inhibitors. Radioiodinated (E)-(131) I-13-iodo-2-methylentridec-12-enoic acid ((131) I-7 c) demonstrated preferential retention in AMACR-positive prostate tumor cells (LNCaP, LNCaP C4-2wt and DU145) compared with both AMACR-knockout LNCaP C4-2 AMACR-siRNA and benign BPH1 prostate cell lines. A significant protein-bound radioactive fraction with main bands at 47 (sum of molecular weights of AMACR plus 12 c), 70, and 75 kDa was detected in LNCaP C4-2 wt cells. In contrast, only negligible amounts of protein-bound radioactivity were found in LNCaP C4-2 AMACR-siRNA cells.

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“…The CACNA1D gene (which encodes a Ca 2+ channel) was up-regulated in prostate cancer, but the larger isoform was more elevated than the smaller isoform, indicating that the gene was differentially regulated at the levels of both transcript abundance and splicing. The AMACR gene (which encodes a-methylacyl-CoA racemase) has recently emerged as a robust biomarker for prostate cancer (46,47). We analyzed the two isoforms resulting from the alternative use of the last exon coupled with alternative polyadenylation (5), and found that whereas one isoform showed a quantitative up-regulation in prostate cancer compared with normal prostatic tissues, the other seemed to be expressed only in prostate cancer.…”

Section: Cancer Researchmentioning

confidence: 99%

Two-Dimensional Transcriptome Profiling: Identification of Messenger RNA Isoform Signatures in Prostate Cancer from Archived Paraffin-Embedded Cancer Specimens

Wang‐Rodriguez²,

Nair³

et al. 2006

Cancer Research

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The expression of specific mRNA isoforms may uniquely reflect the biological state of a cell because it reflects the integrated outcome of both transcriptional and posttranscriptional regulation. In this study, we constructed a splicing array to examine f1,500 mRNA isoforms from a panel of genes previously implicated in prostate cancer and identified a large number of cell type-specific mRNA isoforms. We also developed a novel ''two-dimensional'' profiling strategy to simultaneously quantify changes in splicing and transcript abundance; the results revealed extensive covariation between transcription and splicing in prostate cancer cells. Taking advantage of the ability of our technology to analyze RNA from formalin-fixed, paraffin-embedded tissues, we derived a specific set of mRNA isoform biomarkers for prostate cancer using independent panels of tissue samples for feature selection and crossanalysis. A number of cancer-specific splicing switch events were further validated by laser capture microdissection. Quantitative changes in transcription/RNA stability and qualitative differences in splicing ratio may thus be combined to characterize tumorigenic programs and signature mRNA isoforms may serve as unique biomarkers for tumor diagnosis and prognosis. (Cancer Res 2006; 66(8): 4079-88)

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Alternative spliced variants of the alpha-methylacyl-CoA racemase gene and their expression in prostate cancer

Cited by 27 publications

References 20 publications

Analysis of Prostate-Specific Antigen Transcripts in Chimpanzees, Cynomolgus Monkeys, Baboons, and African Green Monkeys

Analysis of Prostate-Specific Antigen Transcripts in Chimpanzees, Cynomolgus Monkeys, Baboons, and African Green Monkeys

New Molecular Markers for Prostate Tumor Imaging: A Study on 2‐Methylene Substituted Fatty Acids as New AMACR Inhibitors

Two-Dimensional Transcriptome Profiling: Identification of Messenger RNA Isoform Signatures in Prostate Cancer from Archived Paraffin-Embedded Cancer Specimens

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