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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2006-4-10
pubmed:abstractText
Transforming growth factor-beta superfamily has been implicated in tumorigenesis. We have recently shown that Nodal, a member of transforming growth factor-beta superfamily, and its receptor, activin receptor-like kinase 7 (ALK7), inhibit proliferation and induce apoptosis in human epithelial ovarian cancer cell lines. In this study, we further investigated the cellular mechanisms underlying the apoptotic action of ALK7 using an immortalized ovarian surface epithelial cell line, IOSE397, and an epithelial ovarian cancer cell line, OV2008. Infection of these cells with an adenoviral construct carrying constitutively active ALK7 (Ad-ALK7-ca) potently induced cell death; all cells died after 3 and 5 days of Ad-ALK7-ca infection in IOSE397 and OV2008 cells, respectively. ALK7-ca induced the expression of proapoptotic factor Bax but suppressed the expression of antiapoptotic factors Bcl-2, Bcl-XL, and Xiap. Silencing of Bax by small interfering RNA in IOSE397 cells significantly reduced ALK7-ca-induced apoptosis as measured by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay but partially blocked ALK7-ca-induced caspase-3 activation and did not affect the down-regulation of Xiap by ALK7-ca. Dominant-negative Smad2, Smad3, and Smad4 blocked ALK7-ca-regulated Xiap and Bax expression and caspase-3 activation. Thus, ALK7-induced apoptosis is at least in part through two Smad-dependent pathways, Bax/Bcl-2 and Xiap.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1541-7786
pubmed:author
pubmed:issnType
Print
pubmed:volume
4
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
235-46
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:16603637-Activin Receptors, Type I, pubmed-meshheading:16603637-Apoptosis, pubmed-meshheading:16603637-Carcinoma, pubmed-meshheading:16603637-Caspase 3, pubmed-meshheading:16603637-Caspases, pubmed-meshheading:16603637-Cell Line, Tumor, pubmed-meshheading:16603637-Down-Regulation, pubmed-meshheading:16603637-Female, pubmed-meshheading:16603637-Humans, pubmed-meshheading:16603637-Ovarian Neoplasms, pubmed-meshheading:16603637-Ovary, pubmed-meshheading:16603637-RNA, Small Interfering, pubmed-meshheading:16603637-Signal Transduction, pubmed-meshheading:16603637-Smad Proteins, pubmed-meshheading:16603637-Transfection, pubmed-meshheading:16603637-Up-Regulation, pubmed-meshheading:16603637-X-Linked Inhibitor of Apoptosis Protein, pubmed-meshheading:16603637-bcl-2-Associated X Protein
pubmed:year
2006
pubmed:articleTitle
Activin receptor-like kinase 7 induces apoptosis through up-regulation of Bax and down-regulation of Xiap in normal and malignant ovarian epithelial cell lines.
pubmed:affiliation
Department of Biology, York University, 4700 Keel Street, Toronto, Ontario, Canada M3J 1P3.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't