Document Detail

Extracellular pressure stimulates colon cancer cell proliferation via a mechanism requiring PKC and tyrosine kinase signals.
MedLine Citation:
PMID:  15548175     Owner:  NLM     Status:  MEDLINE    
METHODS: Malignant colonocytes on a collagen I matrix were subjected to 15 mmHg pressure. ERK, p38, c-Src and Akt phosphorylation and PKCalpha redistribution were assessed by western blot after 30 min and PKC activation by ELISA. Cells were counted after 24 h and after inhibition of each signal, tyrosine phosphorylation or actin depolymerization.
RESULTS: Pressure time-dependently increased SW620 and HCT-116 cell counts on collagen or fibronectin (P < 0.01). Pressure increased the SW620 S-phase fraction from 28 +/- 1 to 47 +/- 1% (P = 0.0002). Pressure activated p38, ERK, and c-Src (P < 0.05 each) but not Akt/PKB. Pressure decreased cytosolic PKC activity, and translocated PKCalpha to a membrane fraction. Blockade of p38, ERK, c-Src or PI-3-K or actin depolymerization did not inhibit pressure-stimulated proliferation. However, global tyrosine kinase blockade (genistein) and PKC blockade (calphostin C) negated pressure-induced proliferation.
CONCLUSIONS: Extracellular pressure stimulates cell proliferation and activates several signals. However, the mitogenic effect of pressure requires only tyrosine kinase and PKCalpha activation. Pressure may modulate colon cancer growth and implantation by two distinct pathways, one stimulating proliferation and the other promoting adhesion.
M F Walsh; R K-Y Woo; R Gomez; M D Basson
Related Documents :
11395825 - Effect of insufflation gas and intraabdominal pressure on portal venous flow during pne...
3130825 - Variceal bleeding, hypersplenism, and systemic mastocytosis. pathophysiology and manage...
6489275 - A high-pressure injector for sclerotherapy of oesophageal varices.
11539785 - Lymphocyte reactivity during spaceflight.
7032775 - The relative roles of sodium and renin in the hypertension of renal disease. an assessm...
2205195 - Transport aircraft crew and decompression hazards: study of a positive pressure schedule.
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cell proliferation     Volume:  37     ISSN:  0960-7722     ISO Abbreviation:  Cell Prolif.     Publication Date:  2004 Dec 
Date Detail:
Created Date:  2004-11-19     Completed Date:  2005-01-11     Revised Date:  2012-06-25    
Medline Journal Info:
Nlm Unique ID:  9105195     Medline TA:  Cell Prolif     Country:  England    
Other Details:
Languages:  eng     Pagination:  427-41     Citation Subset:  IM    
Wayne State University School of Medicine, John D. Dingell VAMC, Detroit, MI 48201-1932, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Carcinoma / enzymology*,  physiopathology
Cell Adhesion / physiology
Cell Division / physiology
Cell Line, Tumor
Colonic Neoplasms / enzymology*,  physiopathology
Enzyme Inhibitors / pharmacology
Extracellular Fluid / physiology
Extracellular Signal-Regulated MAP Kinases / metabolism
Phosphatidylinositol 3-Kinases / metabolism
Pressure / adverse effects
Protein Kinase C / antagonists & inhibitors,  metabolism*
Protein Kinase C-alpha
Protein Transport / drug effects,  physiology
Protein-Tyrosine Kinases / antagonists & inhibitors,  metabolism*
Signal Transduction / physiology
Time Factors
p38 Mitogen-Activated Protein Kinases / metabolism
Grant Support
Reg. No./Substance:
0/Enzyme Inhibitors; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC Kinases; EC tyrosine-protein kinase; EC protein, human; EC Kinase C; EC Kinase C-alpha; EC Signal-Regulated MAP Kinases; EC Mitogen-Activated Protein Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  3-O-methylfunicone, a secondary metabolite produced by Penicillium pinophilum, induces growth arrest...
Next Document:  Internal thoracic arterial grafts evaluation by multislice CT scan: a preliminary study.