PMID- 10745023
OWN - NLM
STAT- MEDLINE
DCOM- 20000524
LR  - 20161124
IS  - 1044-1549 (Print)
IS  - 1044-1549 (Linking)
VI  - 22
IP  - 4
DP  - 2000 Apr
TI  - Studies on the expression of endothelin, its receptor subtypes, and converting 
      enzymes in lung cancer and in human bronchial epithelium.
PG  - 422-31
AB  - Lung cancer, particularly small cell lung cancer (SCLC), is characterized by 
      production of numerous peptides and their resulting clinical syndromes. Such 
      peptides can act as autocrine growth factors for these tumors. In this study, we 
      investigated the role of endothelin (ET)-1 in lung cancer. Using reverse 
      transcription/polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent 
      assay, and immunocytochemistry, we screened a panel of lung cancer cell lines for 
      ET-1, its receptors, and endothelin converting enzyme-1 (ECE-1), which generates 
      the active form of ET-1. ET-1 messenger RNA was expressed in five of seven SCLC, 
      four of four non-small cell lung cancer (NSCLC), and human bronchial epithelial 
      (HBE) cells. The intracellular isoform of ECE-1, important in processing ET-1 if 
      an autocrine growth loop is to function, was downregulated in the lung cancer 
      cell lines as compared with expression of the extracellular isoform. Endothelin A 
      receptor (ETAR), which mediates the mitogenic effects of ET-1 in prostate and 
      ovarian cancer, was upregulated in HBE cells compared with expression in three of 
      seven SCLC and two of four NSCLC cell lines. Endothelin B receptor (ETBR) was 
      more widespread, being expressed in seven of seven SCLC, four of four NSCLC, and 
      the HBE cells. We used flow cytometry to measure mobilization of intracellular 
      calcium as a functional assay for the ETAR. These data concurred with the RT-PCR 
      results, indicating that the ETAR was downregulated or was involved in an 
      alternative signal transduction pathway in lung cancer, and no evidence of 
      functional receptor mediating an autocrine growth loop was found. From our study, 
      the data do not support the putative functional autocrine growth role of ET-1 in 
      lung cancer. We propose instead that ET-1 may act as a paracrine growth factor 
      for surrounding epithelial and endothelial cells via alternative pathways, 
      promoting angiogenesis and stromal growth.
FAU - Ahmed, S I
AU  - Ahmed SI
AD  - Cancer Research Campaign, Academic Department of Clinical Oncology, University of 
      Nottingham, Nottingham City Hospital, United Kingdom.
FAU - Thompson, J
AU  - Thompson J
FAU - Coulson, J M
AU  - Coulson JM
FAU - Woll, P J
AU  - Woll PJ
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - Am J Respir Cell Mol Biol
JT  - American journal of respiratory cell and molecular biology
JID - 8917225
RN  - 0 (Endothelin-1)
RN  - 0 (Isoenzymes)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Neoplasm)
RN  - 0 (Receptor, Endothelin A)
RN  - 0 (Receptor, Endothelin B)
RN  - 0 (Receptors, Endothelin)
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  - Aspartic Acid Endopeptidases/*biosynthesis/genetics
MH  - *Autocrine Communication
MH  - Bronchi/*metabolism
MH  - Calcium Signaling
MH  - Carcinoma, Non-Small-Cell Lung/genetics/*metabolism
MH  - Carcinoma, Small Cell/genetics/*metabolism
MH  - Endothelin-1/*biosynthesis/genetics
MH  - Endothelin-Converting Enzymes
MH  - Enzyme Induction
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Epithelium/metabolism
MH  - Flow Cytometry
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Isoenzymes/*biosynthesis/genetics
MH  - Lung Neoplasms/genetics/*metabolism
MH  - Metalloendopeptidases
MH  - Microscopy, Fluorescence
MH  - Models, Biological
MH  - Neoplasm Proteins/*biosynthesis/genetics
MH  - RNA, Messenger/biosynthesis
MH  - RNA, Neoplasm/biosynthesis
MH  - Receptor, Endothelin A
MH  - Receptor, Endothelin B
MH  - Receptors, Endothelin/*biosynthesis/genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Tumor Cells, Cultured
EDAT- 2000/04/04 09:00
MHDA- 2000/06/08 09:00
CRDT- 2000/04/04 09:00
PHST- 2000/04/04 09:00 [pubmed]
PHST- 2000/06/08 09:00 [medline]
PHST- 2000/04/04 09:00 [entrez]
AID - 10.1165/ajrcmb.22.4.3795 [doi]
PST - ppublish
SO  - Am J Respir Cell Mol Biol. 2000 Apr;22(4):422-31. doi: 10.1165/ajrcmb.22.4.3795.