A fourth isoform of endothelin‐converting enzyme (ECE‐1) is generated from an additional promoter

Valdenaire, Olivier; Lepailleur-Enouf, Delphine; Egidy, Giorgia; Thouard, Anne; Barret, Alain; Vranckx, Roger; Tougard, Claude; Michel, Jean‐Baptiste

doi:10.1046/j.1432-1327.1999.00602.x

Cited by 160 publications

(156 citation statements)

References 40 publications

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“…12 Of the three peptides, ET-1 is the most abundant peptide in most tissue specimens and is bound by both ET A and ET B . Most of the effects triggered by ET-1 are mediated by the ET A receptor (e.g., vasoconstriction, mitogenesis, resistance to apoptosis, and pain), whereas the ET B receptor appears to signal opposing actions (e.g., vasodilation or analgesia).…”

Section: Discussionmentioning

confidence: 99%

“…These include the hypervascular nature of ccRCC compared with the characteristically hypovascular appearance of PRCC, the presence of infiltrating lymphocytes and macrophages in PRCC but not in ccRCC, and the increased incidence of necrosis in patients with PRCC but not in patients with ccRCC. Distinct karyotypic aberrations also set these subtypes apart, such as loss of 3p in ccRCC compared with trisomies of 7,12,16,17, and 20 and loss of the Y chromosome in PRCC. 2,5,6 The endothelin axis comprises three endothelin peptides (ET-1, ET-2, and ET-3) and two cell-surface receptors (ET A and ET B ).…”

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confidence: 99%

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Endothelin axis expression is markedly different in the two main subtypes of renal cell carcinoma

Douglas

Richardson

Nicol

2004

Cancer

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BACKGROUNDThe endothelin axis has been implicated in cancer growth, angiogenesis, and metastasis, but to the authors' knowledge the expression of endothelin genes has not been defined in renal cell carcinoma (RCC).METHODSTissue specimens were harvested from both normal and tumor‐affected regions at the time of radical nephrectomy from 35 patients with RCC (22 with clear cell RCC [ccRCC] and 13 with papillary RCC [PRCC]). Real‐time reverse transcriptase‐polymerase chain reaction analysis determined the expression profile of the preproendothelins (PPET‐1, PPET‐2, and PPET‐3), the endothelin receptors (ETA and ETB), and the endothelin‐converting enzymes (ECE‐1 and ECE‐2).RESULTSPPET‐1 was found to be up‐regulated in ccRCC tumor specimens and down‐regulated in PRCC tumor specimens. ETA was significantly down‐regulated in PRCC tumor specimens. ECE‐1 was expressed in all tissue specimens at comparable levels, with moderate but significant elevation in normal tissue specimens associated with PRCC. Of the other genes, PPET‐2 and ETB were expressed in all tissue specimens and no differences were observed between tumor subtypes or tumor‐affected and normal tissue specimens, whereas PPET‐3 and ECE‐2 were present in all tissue specimens but were barely detectable.CONCLUSIONSThe endothelin axis was expressed differently in the two main subtypes of RCC and appeared to match macroscopic features commonly observed in these tumors (i.e., high expression of PPET‐1 in hypervascular ccRCC contrasted against low PPET‐1 and ETA expression in hypovascular PRCC). The presence of ECE‐1 mRNA in these tissue specimens suggested that active endothelin ligands were present, indicating endothelin axis activity was elevated in ccRCC compared with normal kidney, but impaired in PRCC. The current study provided further evidence that it is not appropriate to consider ccRCC and PRCC indiscriminately in regard to treatment. Cancer 2004. © 2004 American Cancer Society.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Endothelin axis expression is markedly different in the two main subtypes of renal cell carcinoma

Douglas

Richardson

Nicol

2004

Cancer

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“…Endothelin-converting enzyme-1 is a membrane-bound zincdependent metallopeptidase of the M13 family, which also includes the closely related peptidase, neutral endopeptidase (NEP, CALLA, CD10) (Turner et al, 2001). Endothelin-converting enzyme-1 has a broad tissue distribution and exists as four distinct isoforms termed ECE-1a, ECE-1b, ECE-1c (Schweizer et al, 1997) and ECE1d (Valdenaire et al, 1999). These isoforms differ only in their Nterminal regions and are derived from a single gene through the use of alternative promoters.…”

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Stromal–epithelial interactions influence prostate cancer cell invasion by altering the balance of metallopeptidase expression

et al. 2004

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Perturbations of stromal -epithelial interactions in the developing tumour can contribute to cancer invasion and metastasis. The structurally related metallopeptidases endothelin-converting enzyme (ECE) and neutral endopeptidase (NEP) contribute sequentially to the synthesis and inactivation of ET-1, a mitogenic peptide that has been shown to affect tumour behaviour. This study has investigated the interaction between metastatic tumour epithelial cells, which lack NEP, and stromal cells, which we have shown to express ECE-1 (stromal -epithelial interactions), using Matrigel invasion chambers. The epithelial cell lines utilised in this study include androgen-sensitive LNCaP, androgen-independent PC-3, Du145 and recently established PNT-1a, PNT2-C2 and P4E6 prostate cell lines. Specific inhibition of endogenous ECE-1 activity in stromal cells reduced PC-3 and Du145 invasion by 70 and 50%, respectively. Addition of recombinant NEP to inactivate endogenous mitogenic peptides resulted in 50 and 20% reductions in invasion in PC-3 and Du145 cells, respectively. Neutral endopeptidase effects were reversed in the presence of thiorphan, a specific NEP inhibitor. Supplementation of defined media with bradykinin and ET-1 significantly increased PC-3 invasion by 40 and 50%, respectively. Du145 cell invasion increased by approximately 100% on adding ET-1. These studies implicate the metallopeptidases NEP and ECE-1 as mediators of prostate cancer invasion via a stromal/epithelial interaction.

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“…They are then cleaved by endothelin-converting enzyme (ECE-1) to yield the active peptides (Shimada et al, 1995). At least 4 isoforms, ECE-1 a-d have been characterized (Valdenaire et al, 1999). ET act on two distinct high-affinity receptor subtypes, ET A (Arai et al, 1990) and ET B (Sakurai et al, 1990), which belong to the seven transmembrane G-protein-coupled receptor family.…”

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The Endothelin System in Human Glioblastoma

Egidy

Eberl

Valdenaire

et al. 2000

Laboratory Investigation

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SUMMARY:Endothelin-1 (ET-1) is a powerful mitogenic and/or anti-apoptotic peptide produced by many cancer cells. To evaluate the potential role of the endothelin system in glioblastoma we first determined the cellular distribution of the mRNA and proteins of the components of the endothelin system, preproendothelin-1 (PPET-1), endothelin-converting enzyme-1 (ECE-1), and ET A and ET B receptors in human glioblastoma tissue and glioblastoma cell lines. PPET-1, ECE-1, and ET A receptor were highly expressed in glioblastoma vessels and in some scattered glioblastoma areas whereas ET B receptor was mainly found in cancer cells. This suggests that glioblastoma vessels constitute an important source of ET-1 that acts on cancer cells via the ET B receptor. Four human glioblastoma cell lines expressed mRNA for all of the components of the ET-1 pathway. Bosentan, a mixed ET A and ET B receptor antagonist, induced apoptosis in these cell lines in a dose-dependent manner. Apoptosis was potentiated by Fas Ligand (APO-1L, CD95L), a pro-apoptotic peptide, only in LNZ308 cells, corresponding to the known functional Fas expression in these cell lines. LNZ308 cells also expressed the long and short forms of the cellular FLICE/caspase-8 inhibitory protein (FLIP). Bosentan and a protein kinase C inhibitor down-regulated short FLIP in these cells. ET-1 induced transient phosphorylation of extracellular signal-regulated kinase but did not induce long-term thymidine incorporation in LNZ308 glioblastoma cells. These results suggest that, in glioblastoma cells, ET-1, mainly acting via the ET B receptor, is a survival/antiapoptotic factor produced by tumor vasculature, but not a proliferation factor, involving protein kinase C and extracellular signal-regulated kinase pathways, and stabilization of the short form of FLIP. (Lab Invest 2000, 80:1681-1689.

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A fourth isoform of endothelin‐converting enzyme (ECE‐1) is generated from an additional promoter

Cited by 160 publications

References 40 publications

Endothelin axis expression is markedly different in the two main subtypes of renal cell carcinoma

Endothelin axis expression is markedly different in the two main subtypes of renal cell carcinoma

Stromal–epithelial interactions influence prostate cancer cell invasion by altering the balance of metallopeptidase expression

The Endothelin System in Human Glioblastoma

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