PMID- 16007684 OWN - NLM STAT- MEDLINE DCOM- 20050929 LR - 20161124 IS - 0008-543X (Print) IS - 0008-543X (Linking) VI - 104 IP - 5 DP - 2005 Sep 1 TI - Localization of the endothelin system in human diffuse astrocytomas. PG - 1049-57 AB - BACKGROUND: Endothelin-1 (ET-1), a vasoconstrictor and mitogen, has recently been implicated in the pathogenesis of human glioblastoma, neuroblastoma, and meningioma. ET-1, formed by proteolysis of the propeptide big ET-1 by endothelin-converting enzyme-1 (ECE-1), mediates its cellular actions through ETA and ETB receptors. Because only immunoreactive ET-1 has been observed within human astrocytic tumor cells, the authors investigated the localization of the entire ET-1 system (ET-1 mRNA, ET-1, ECE-1, ETA and ETB receptors) in surgical samples of human diffuse astrocytomas WHO Grade II (n = 6). METHODS: ET-1 mRNA expression was elucidated by in situ reverse transcriptase polymerase chain reaction (RT-PCR) using synthetic primers. Polyclonal antibodies were used to localize ET-1, ECE-1, ETA and ETB receptors by immunocytochemistry. RESULTS: All ET components were detected in the six tumor samples. Intense (3+) cytoplasmic ET-1 mRNA labeling was observed in more than 75% of cells in all 6 astrocytomas. Up to 75% of tumor cells displayed intense ET-1 and ECE-1 immunolabeling distributed throughout their cytoplasm. Immunoreactive ETA and ETB receptors, observed in 25% to 75% of astrocytic tumor cells, were of moderate intensity. In addition, all components of the ET system were seen within endothelial cells of tumor blood vessels. CONCLUSIONS: The presence of ET-1 mRNA, ECE-1, and ET-1 within tumor astrocytes suggests local ET synthesis and processing. The mitogenic and antiapoptotic properties of ET-1, as well as the vasodilatory signaling of ETB receptors, may promote tumorigenesis. FAU - Naidoo, Vinogran AU - Naidoo V AD - Department of Pharmacology, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa. FAU - Naidoo, Strinivasen AU - Naidoo S FAU - Mahabeer, Rajeshree AU - Mahabeer R FAU - Raidoo, Deshandra M AU - Raidoo DM LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Cancer JT - Cancer JID - 0374236 RN - 0 (Endothelin-1) RN - 0 (RNA, Messenger) RN - 0 (Receptor, Endothelin A) RN - 0 (Receptor, Endothelin B) RN - EC 3.4.23.- (Aspartic Acid Endopeptidases) RN - EC 3.4.24.- (Metalloendopeptidases) RN - EC 3.4.24.71 (ECE1 protein, human) RN - EC 3.4.24.71 (Endothelin-Converting Enzymes) SB - IM MH - Adult MH - Aspartic Acid Endopeptidases/*analysis MH - Astrocytoma/*chemistry/etiology MH - Endothelin-1/*analysis/genetics/physiology MH - Endothelin-Converting Enzymes MH - Female MH - Humans MH - Immunohistochemistry MH - Male MH - Metalloendopeptidases/*analysis MH - RNA, Messenger/analysis MH - Receptor, Endothelin A/*analysis MH - Receptor, Endothelin B/*analysis MH - Reverse Transcriptase Polymerase Chain Reaction EDAT- 2005/07/12 09:00 MHDA- 2005/09/30 09:00 CRDT- 2005/07/12 09:00 PHST- 2005/07/12 09:00 [pubmed] PHST- 2005/09/30 09:00 [medline] PHST- 2005/07/12 09:00 [entrez] AID - 10.1002/cncr.21277 [doi] PST - ppublish SO - Cancer. 2005 Sep 1;104(5):1049-57. doi: 10.1002/cncr.21277.