Linked Life Data

19711341

Source:http://linkedlifedata.com/resource/pubmed/id/19711341

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2010-2-3
pubmed:abstractText
We have recently demonstrated that BEX2 is differentially expressed in primary breast tumors and BEX2 expression is required for the Nerve Growth factor inhibition of ceramide-induced apoptosis in breast cancer. In this study we investigate the functional role of BEX2 in the survival and growth of breast cancer cells. We demonstrate that BEX2 downregulation induces mitochondrial apoptosis and sensitizes breast cancer cells to the pro-apoptotic effects of ceramide, doxorubicin and staurosporine. In addition, BEX2 overexpression protects the breast cancer cells against mitochondrial apoptosis. We show that this effect of BEX2 is mediated through the modulation of Bcl-2 protein family, which involves the positive regulation of anti-apoptotic member Bcl-2 and the negative regulation of pro-apoptotic members BAD, BAK1 and PUMA. Moreover, our data suggests that BEX2 expression is required for the normal cell cycle progression during G1 in breast cancer cells through the regulation of cyclin D1 and p21. To further support the significance of BEX2 in the pathogenesis of breast cancer we demonstrate that BEX2 overexpression is associated with a higher activation of the Bcl-2/NF-kappaB pathway in primary breast tumors. Furthermore, we show that BEX2 downregulation results in a higher expression and activity of protein phosphatase 2A. The modulation of protein phosphatase 2A, which is also known to mediate the cellular response to ceramide, provides a possible mechanism to explain the BEX2-mediated cellular effects. This study demonstrates that BEX2 has a significant role in the regulation of mitochondrial apoptosis and G1 cell cycle in breast cancer.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1097-0215
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
126
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1596-610
pubmed:meshHeading
pubmed-meshheading:19711341-Apoptosis, pubmed-meshheading:19711341-Blotting, Western, pubmed-meshheading:19711341-Breast Neoplasms, pubmed-meshheading:19711341-Cell Line, Tumor, pubmed-meshheading:19711341-Cyclin-Dependent Kinase Inhibitor p21, pubmed-meshheading:19711341-Down-Regulation, pubmed-meshheading:19711341-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:19711341-Flow Cytometry, pubmed-meshheading:19711341-Fluorescent Antibody Technique, pubmed-meshheading:19711341-G1 Phase, pubmed-meshheading:19711341-Humans, pubmed-meshheading:19711341-Immunoenzyme Techniques, pubmed-meshheading:19711341-Mitochondria, pubmed-meshheading:19711341-NF-kappa B, pubmed-meshheading:19711341-Nerve Tissue Proteins, pubmed-meshheading:19711341-Phosphorylation, pubmed-meshheading:19711341-Protein Phosphatase 2, pubmed-meshheading:19711341-Proto-Oncogene Proteins c-bcl-2, pubmed-meshheading:19711341-RNA, Messenger, pubmed-meshheading:19711341-RNA, Small Interfering, pubmed-meshheading:19711341-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:19711341-Synaptotagmin I
pubmed:year
2010
pubmed:articleTitle
BEX2 regulates mitochondrial apoptosis and G1 cell cycle in breast cancer.
pubmed:affiliation
The University of Queensland Diamantina Institute, Princess Alexandra Hospital, Brisbane Qld 4102, Australia. a.naderi@uq.edu.au
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't