Tissue-specificity of prostate specific antigens: Comparative analysis of transcript levels in prostate and non-prostatic tissues

Cunha, Ana C.; Weigle, Bernd; Kießling, Andrea; Bachmann, Michael; Rieber, Ernst Peter

doi:10.1016/j.canlet.2005.05.021

Cited by 122 publications

(108 citation statements)

References 31 publications

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“…3a) but undetectable in other cell types (representative HUVEC is shown in Fig. 3b [29,30]). We then showed that introduction of exogenous synthetic miR-126*-mimic in LNCaP cells silenced prostein protein expression, while the mRNA level remained unaffected (Fig.…”

Section: Prostein Is a Specific Target Of Ectopic Mir-126*mentioning

confidence: 99%

“…We show that prostate cells are naturally deficient in miR-126*, supporting recent miRNA tissue profiling [28] and that this is due to poor Egfl7 gene expression. In contrast, prostate cells are famously enriched in a number of prostate-specific antigens that includes the most recently discovered protein, prostein (NM_033102), also called prostate cancer-associated protein 6 (PCANAP6) and solute carrier family 45, member 3 (SLC45A3) [29,30]. We postulated that the scarcity of miR-126* in the prostate might be causally related to the abundance of prostein in this tissue.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Ectopic expression of miR-126*, an intronic product of the vascular endothelial EGF-like 7 gene, regulates prostein translation and invasiveness of prostate cancer LNCaP cells

2008

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MicroRNAs (miRNAs) are endogenous noncoding RNAs that down-regulate gene expression by promoting cleavage or translational arrest of target mRNAs. While most miRNAs are transcribed from their own dedicated genes, some map to introns of 'host' transcripts, the biological significance of which remains unknown. Here, we show that prostate cells are naturally devoid of EGF-like domain 7 (Egfl7) transcripts and hence also deficient in a miRNA, miR-126*, generated from splicing and processing of its ninth intron. Use of recombinant and synthetic miRNAs or a specific antagomir established a role of miR-126* in silencing prostein in non-endothelial cells. We mapped two miR-126*-binding sites in the 3′UTR of the prostein mRNA required for translational repression. Transfection of synthetic miR-126* into prostate cancer LNCaP cells strongly reduced the translation of prostein. Interestingly, loss of prostein correlated with reduction of LNCaP cell migration and invasion. Thus, the robust expression of prostein protein in the prostate cells results from a combination of transcriptional activation of the prostein gene and absence of intronic miRNA-126* due to the prostate-specific repression of the Egfl7 gene. We conclude that intronic miRNAs from tissue-specific transcripts, or their natural absence, make cardinal contributions to cellular gene expression and phenotype. These findings also open the door to tissue-specific miRNA therapy.

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Section: Prostein Is a Specific Target Of Ectopic Mir-126*mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Ectopic expression of miR-126*, an intronic product of the vascular endothelial EGF-like 7 gene, regulates prostein translation and invasiveness of prostate cancer LNCaP cells

2008

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“…Data from immunohistochemistry (IHC) studies indicate that > 95% of normal adult prostate tissue samples, including normal tissue adjacent to tumor, strongly express PAP [5,11,12]. Analyses of PAP mRNA levels by RNA blotting methods [13] and quantitative polymerase chain reaction (qPCR) using pooled tissue samples [14] indicate high levels of PAP mRNA expression in normal prostate tissue. PAP has generally been considered a tissue-specific prostate antigen, highly expressed in both normal and malignant prostate cells.…”

Section: Introductionmentioning

confidence: 99%

“…Using qPCR to measure relative levels of PAP mRNA transcripts, Cunha and colleagues [14] found that, relative to prostate, PAP mRNA was expressed at low levels in several normal tissues, most notably in placenta, kidney, and testis. The kidney expression levels were 192-fold less (0.5%) than those seen in normal prostate tissue.…”

Section: Introductionmentioning

confidence: 99%

Prostatic acid phosphatase expression in human tissues

Graddis

McMahan

Tamman³

et al. 2010

Clinical Cancer Research

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Prostate cancer is the most common cancer and the second leading cause of cancer deaths among males in most Western countries. Autologous cellular immunotherapy for the treatment of cancer seeks to induce tumorspecific immunity in the patient and is consequently dependent on a suitable target antigen and effective presentation of that antigen to the patient's immune system. Prostatic acid phosphatase (PAP) has been tested as a target antigen due to its high and apparently specific expression in the prostate. We used a variety of approaches to analyze PAP expression, including immunohistochemistry, in situ hybridization, and quantitative polymerase chain reaction. We complemented these laboratory-based techniques with an in silico analysis of reported PAP expression in human cDNA libraries. Our studies confirmed that, while PAP expression is not restricted to prostate tissues, its expression in other human tissues is approximately 1-2 orders of magnitude less than that observed in the prostate. The relative specificity of PAP expression in the prostate supports its use as a target of autologous cellular immunotherapy. The approach described here, involving the use of multiple correlates of tissue-specific expression, is warranted as a prerequisite in selecting any suitable target for immunotherapy.

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“…PMEPAI was initially described as a novel androgen-regulated gene abundantly expressed in normal and malignant prostate tissue and in androgen-independent tissues (15,25). Increased PMEPAI expression was later noted also in renal and other cancers (23)(24)(25)(26). Further characterization of the PMEPAI expression in advanced or hormonerefractory CaP tissue, or both, is warranted.…”

Section: G-protein-coupled Olfactory Receptor (Psgr)mentioning

confidence: 99%

Prostate — Specific G Protein Couple Receptor Genes and STAG1/PMEPA1 in Peripheral Blood from Patients with Prostatic Cancer

Mr¹,

F²

2006

Int J Immunopathol Pharmacol

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We investigated whether prostate - specific G protein couple receptor genes (PSGR) and STAG1/PMEPA1 gene expression in peripheral- blood could be useful as a diagnostic or prognostic marker of prostate cancer. Circulating cells were identified by reverse transcription-polymerase chain reaction (RT-PCR) to detect PSGR and STAG1/PMEPA1 mRNA in peripheral blood (PB) from 11 patients with treated prostate cancer (CaP), 11 with newly-diagnosed untreated CaP and 20 with benign prostatic hyperplasia (BPH) (controls). RT-PCR amplified PSGR in 8 of 11 untreated and in 9 of 11 treated patients with CaP and in 16 of 20 with BPH; whereas it amplified PMEPA1 in 1 of 11 untreated and in 7 of 11 treated patients with CaP and in 4 of 20 with BPH. In our control tissues and cell lines nearly all the prostatic and non- prostatic tissues and cell lines expressed PSGR mRNA, whereas only one prostatic neoplastic tissue and the androgen-responsive (LNCaP) and androgen non-responsive (PC3) prostatic cell lines expressed PMEPA1. These findings suggest that the investigated genes are poorly specific and probably of little use as diagnostic or prognostic markers in peripheral blood for monitoring prostate cancer progression and recurrence.

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Tissue-specificity of prostate specific antigens: Comparative analysis of transcript levels in prostate and non-prostatic tissues

Cited by 122 publications

References 31 publications

Ectopic expression of miR-126*, an intronic product of the vascular endothelial EGF-like 7 gene, regulates prostein translation and invasiveness of prostate cancer LNCaP cells

Ectopic expression of miR-126*, an intronic product of the vascular endothelial EGF-like 7 gene, regulates prostein translation and invasiveness of prostate cancer LNCaP cells

Prostatic acid phosphatase expression in human tissues

Prostate — Specific G Protein Couple Receptor Genes and STAG1/PMEPA1 in Peripheral Blood from Patients with Prostatic Cancer

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