Document Detail

The intrinsic mitochondrial membrane potential (Deltapsim) is associated with steady-state mitochondrial activity and the extent to which colonic epithelial cells undergo butyrate-mediated growth arrest and apoptosis.
MedLine Citation:
PMID:  14559818     Owner:  NLM     Status:  MEDLINE    
Transformation of colonic epithelial cells is characterized by decreased mitochondrial activity, increased mitochondrial membrane potential (Deltapsi(m)), and disruptions in the equilibrium between cell proliferation and death by apoptosis. We have previously shown that an intact Deltapsi(m) is essential for growth arrest and apoptosis induced by butyrate, a physiological regulator of maturation in these cells, suggesting a role for the Deltapsi(m) in the initiation and integration of proliferation and apoptotic pathways. To extend this work, we have generated isogenic cell lines, from SW620 human colonic carcinoma cells, which exhibit significant differences in intrinsic Deltapsi(m). These differences in Deltapsi(m) are not linked to alterations in viability, Bcl-2 levels, or the differentiation status of the cells. However, compared with parental cells and those with increased Deltapsi(m), cells with decreased intrinsic Deltapsi(m) exhibit significantly higher levels of steady-state mitochondrial mRNA and butyrate-induced p21(WAF1/Cip1) and G(0)-G(1) arrest. Moreover, despite butyrate-mediated translocation of proapoptotic Bax and Bak to the mitochondria, fewer cells with elevated intrinsic Deltapsi(m) exhibit concomitant cytochrome c release, and cells with elevated Deltapsi(m) undergo significantly lower levels of Deltapsi(m) dissipation and apoptosis than parental cells, or cells with decreased Deltapsi(m). Homeostasis of the colonic mucosa depends on balancing cell proliferation with apoptosis, and mitochondrial abnormalities are associated with disruptions in this balance. Thus, by affecting steady-state mitochondrial activity and the extent to which cells enter growth arrest and apoptotic cascades, these data establish a role for the intrinsic Deltapsi(m) in contributing to the probability of colonic tumorigenesis and progression.
Barbara G Heerdt; Michele A Houston; Andrew J Wilson; Leonard H Augenlicht
Related Documents :
19597348 - Downregulation of a mitochondria associated protein slp-2 inhibits tumor cell motility,...
18097588 - Differential involvement of mitochondria during ursolic acid-induced apoptotic process ...
19749178 - Overexpression of mitochondrial leishmania major ascorbate peroxidase enhances toleranc...
15751778 - Changes in mitochondrial rna production in cells treated with nucleoside analogues.
24361178 - Redirection of doublecortin-positive cell migration by over-expression of the chemokine...
19649148 - Current concepts of metastasis in melanoma.
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cancer research     Volume:  63     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  2003 Oct 
Date Detail:
Created Date:  2003-10-15     Completed Date:  2003-12-03     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  6311-9     Citation Subset:  IM    
Department of Oncology, Albert Einstein Cancer Center, Montefiore Medical Center, 111 East 210th Street, Bronx, NY 10467, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Apoptosis / drug effects,  physiology
Butyrates / pharmacology*
Cell Division / drug effects,  physiology
Cell Line, Tumor
Colonic Neoplasms / pathology*
Cytochromes c / metabolism,  secretion
Intracellular Membranes / drug effects,  physiology
Membrane Potentials / drug effects,  physiology
Membrane Proteins / metabolism
Mitochondria / drug effects,  genetics,  metabolism,  physiology*
Proto-Oncogene Proteins / metabolism
Proto-Oncogene Proteins c-bcl-2 / metabolism
RNA, Messenger / genetics,  metabolism
bcl-2 Homologous Antagonist-Killer Protein
bcl-2-Associated X Protein
Grant Support
Reg. No./Substance:
0/BAK1 protein, human; 0/BAX protein, human; 0/Butyrates; 0/Membrane Proteins; 0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-bcl-2; 0/RNA, Messenger; 0/bcl-2 Homologous Antagonist-Killer Protein; 0/bcl-2-Associated X Protein; 9007-43-6/Cytochromes c

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

Previous Document:  Methylation-associated silencing of the thrombospondin-1 gene in human neuroblastoma.
Next Document:  Involvement of TSLC1 in progression of esophageal squamous cell carcinoma.