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Initiation of human colon cancer cell proliferation by trypsin acting at protease-activated receptor-2
Authors
Akers IA
Aldenborg F
+56 more
Augeron C
Belham CM
Bernard-Perrone F
Blackhart BD
Blasi F
Blumberg PM
Bohm SK
Bohm SK
Bustos D
Carney DH
Chirgwin JM
D&rsquo
Darmoul D
DeFea KA
Dery O
Green GM
Hedstrom J
Hirahara F
Hollenberg MD
Hollenberg MD
Ichikawa Y
Ishihara H
Kawano N
Kennedy AR
Kennedy AR
Kong W
Koshikawa N
Koshikawa N
Koshikawa N
Laburthe M
Maoret JJ
Mazzieri R
McCawley LJ
Mignatti P
Mirza H
Miyata S
Miyata S
Molino M
Molino M
Molino M
Nguyen TD
Normanno N
Nystedt S
Nystedt S
O&rsquo
Ramos-DeSimone N
Saifeddine M
Singh P
Singh P
Smith R
Sorsa T
Vergnolle N
Vergnolle N
Vu TK
Xu WF
Yu Z
Publication date
Publisher
Nature Publishing Group
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on
PubMed
Abstract
The protease-activated receptor-2 (PAR-2) is a G protein-coupled receptor that is cleaved and activated by trypsin. We investigated the expression of PAR-2 and the role of trypsin in cell proliferation in human colon cancer cell lines. A total of 10 cell lines were tested for expression of PAR-2 mRNA by Northern blot and RT-PCR. PAR-2 protein was detected by immunofluorescence. Trypsin and the peptide agonist SLIGKV (AP2) were tested for their ability to induce calcium mobilization and to promote cell proliferation on serum-deprived cells. PAR-2 mRNA was detected by Northern blot analysis in 6 out of 10 cell lines [HT-29, Cl.19A, Caco-2, SW480, HCT-8 and T84]. Other cell lines expressed low levels of transcripts, which were detected only by RT-PCR. Further results were obtained with HT-29 cells: (1) PAR-2 protein is expressed at the cell surface; (2) an increase in intracellular calcium concentration was observed upon trypsin (1–100 nM) or AP2 (10–100 μM) challenges; (3) cells grown in serum-deprived media supplemented with trypsin (0.1–1 nM) or AP2 (1–300 μM) exhibited important mitogenic responses (3-fold increase of cell number). Proliferative effects of trypsin or AP2 were also observed in other cell lines expressing PAR-2. These data show that subnanomolar concentrations of trypsin, acting at PAR-2, promoted the proliferation of human colon cancer cells. The results of this study indicate that trypsin could be considered as a growth factor and unravel a new mechanism whereby serine proteases control colon tumours. © 2001 Cancer Research Campaign http://www.bjcancer.co
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Last time updated on 04/12/2019