Linked Life Data

14724575

Source:http://linkedlifedata.com/resource/pubmed/id/14724575

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2004-1-15
pubmed:abstractText
Anoikis is the apoptotic response induced in normal cells by inadequate or inappropriate adhesion to substrate. It is postulated that resistance to anoikis facilitates tumorigenesis and metastasis. Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is an immunoglobulin superfamily member overexpressed in a number of human cancers and implicated in anoikis resistance. We tested the effect of CEACAM6 gene silencing on anoikis in pancreatic adenocarcinoma cell lines. Anoikis was induced in PANC1, Capan2, MiaPaCa2 and Mia(AR) (a MiaPaCa2-derived anoikis-resistant subline) by culture in poly-2-hydroxyethylmethacrylate-coated wells. Anoikis was quantified by YO-PRO-1/propidium iodide staining and flow cytometry. The role of caspase activation was determined using fluorometric profiling and the caspase inhibitor Z-Val-Ala-Asp-fluoromethyl ketone (Z-VAD-fmk). CEACAM6 expression was suppressed by RNA interference. Using a nude mouse orthotopic xenograft model, we assessed the effect of this treatment on in vivo metastatic ability. Anoikis resistance was associated with increased CEACAM6 expression. CEACAM6-specific short interfering ribonucleic acid (siRNA), but not control siRNA, increased susceptibility to caspase-mediated anoikis, an effect abrogated by Z-VAD-fmk, and decreased Akt phosphorylation (Ser-473) under anchorage-independent conditions. CEACAM6 gene silencing reversed the acquired anoikis resistance of Mia(AR) and inhibited its in vivo metastatic ability. CEACAM6 warrants further investigation as a novel therapeutic target for the treatment of pancreatic adenocarcinoma.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
465-73
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:14724575-Adenocarcinoma, pubmed-meshheading:14724575-Animals, pubmed-meshheading:14724575-Anoikis, pubmed-meshheading:14724575-Antigens, CD, pubmed-meshheading:14724575-Antigens, Neoplasm, pubmed-meshheading:14724575-Caspases, pubmed-meshheading:14724575-Cell Adhesion Molecules, pubmed-meshheading:14724575-Cell Division, pubmed-meshheading:14724575-Cell Line, Tumor, pubmed-meshheading:14724575-GPI-Linked Proteins, pubmed-meshheading:14724575-Gene Silencing, pubmed-meshheading:14724575-Humans, pubmed-meshheading:14724575-Liver Neoplasms, pubmed-meshheading:14724575-Mice, pubmed-meshheading:14724575-Mice, Nude, pubmed-meshheading:14724575-Neoplasm Metastasis, pubmed-meshheading:14724575-Neoplasm Transplantation, pubmed-meshheading:14724575-Oncogene Protein v-akt, pubmed-meshheading:14724575-Pancreatic Neoplasms, pubmed-meshheading:14724575-RNA, Messenger, pubmed-meshheading:14724575-RNA, Small Interfering, pubmed-meshheading:14724575-Retroviridae Proteins, Oncogenic
pubmed:year
2004
pubmed:articleTitle
CEACAM6 gene silencing impairs anoikis resistance and in vivo metastatic ability of pancreatic adenocarcinoma cells.
pubmed:affiliation
Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't