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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2008-4-14
pubmed:abstractText
Deregulation of apoptotic pathways plays a central role in cancer pathogenesis. X-linked inhibitor of apoptosis protein (XIAP), is an antiapoptotic molecule, whose elevated expression has been observed in tumor specimens from patients with prostate carcinoma. Studies in human cancer cell culture models and xenograft tumor models have demonstrated that loss of XIAP sensitizes cancer cells to apoptotic stimuli and abrogates tumor growth. In view of these findings, XIAP represents an attractive antiapoptotic therapeutic target for prostate cancer. To examine the role of XIAP in an immunocompetent mouse cancer model, we have generated transgenic adenocarcinoma of the mouse prostate (TRAMP) mice that lack XIAP. We did not observe a protective effect of Xiap deficiency in TRAMP mice as measured by tumor onset and overall survival. In fact, there was an unexpected trend toward more aggressive disease in the Xiap-deficient mice. These findings suggest that alternative mechanisms of apoptosis resistance are playing a significant oncogenic role in the setting of Xiap deficiency. Our study has implications for XIAP-targeting therapies currently in development. Greater understanding of these mechanisms will aid in combating resistance to XIAP-targeting treatment, in addition to optimizing selection of patients who are most likely to respond to such treatment.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/18259199-10647931, http://linkedlifedata.com/resource/pubmed/commentcorrection/18259199-10797013, http://linkedlifedata.com/resource/pubmed/commentcorrection/18259199-10815900, http://linkedlifedata.com/resource/pubmed/commentcorrection/18259199-10962579, http://linkedlifedata.com/resource/pubmed/commentcorrection/18259199-11059757, http://linkedlifedata.com/resource/pubmed/commentcorrection/18259199-11077442, http://linkedlifedata.com/resource/pubmed/commentcorrection/18259199-11313486, http://linkedlifedata.com/resource/pubmed/commentcorrection/18259199-11445667, http://linkedlifedata.com/resource/pubmed/commentcorrection/18259199-11489828, http://linkedlifedata.com/resource/pubmed/commentcorrection/18259199-11504910, http://linkedlifedata.com/resource/pubmed/commentcorrection/18259199-12086884, http://linkedlifedata.com/resource/pubmed/commentcorrection/18259199-12218061, http://linkedlifedata.com/resource/pubmed/commentcorrection/18259199-12455050, http://linkedlifedata.com/resource/pubmed/commentcorrection/18259199-12481428, http://linkedlifedata.com/resource/pubmed/commentcorrection/18259199-12624662, http://linkedlifedata.com/resource/pubmed/commentcorrection/18259199-14581366, http://linkedlifedata.com/resource/pubmed/commentcorrection/18259199-14583479, http://linkedlifedata.com/resource/pubmed/commentcorrection/18259199-14749124, http://linkedlifedata.com/resource/pubmed/commentcorrection/18259199-15126334, http://linkedlifedata.com/resource/pubmed/commentcorrection/18259199-15126378, http://linkedlifedata.com/resource/pubmed/commentcorrection/18259199-15173080, http://linkedlifedata.com/resource/pubmed/commentcorrection/18259199-15210856, http://linkedlifedata.com/resource/pubmed/commentcorrection/18259199-15337122, http://linkedlifedata.com/resource/pubmed/commentcorrection/18259199-15378029, http://linkedlifedata.com/resource/pubmed/commentcorrection/18259199-15578516, http://linkedlifedata.com/resource/pubmed/commentcorrection/18259199-15580265, http://linkedlifedata.com/resource/pubmed/commentcorrection/18259199-15781653, http://linkedlifedata.com/resource/pubmed/commentcorrection/18259199-15803136, http://linkedlifedata.com/resource/pubmed/commentcorrection/18259199-16115895, http://linkedlifedata.com/resource/pubmed/commentcorrection/18259199-16322751, http://linkedlifedata.com/resource/pubmed/commentcorrection/18259199-16339151, http://linkedlifedata.com/resource/pubmed/commentcorrection/18259199-16452233, http://linkedlifedata.com/resource/pubmed/commentcorrection/18259199-16799641, http://linkedlifedata.com/resource/pubmed/commentcorrection/18259199-16951243, http://linkedlifedata.com/resource/pubmed/commentcorrection/18259199-17257402, http://linkedlifedata.com/resource/pubmed/commentcorrection/18259199-17311258, http://linkedlifedata.com/resource/pubmed/commentcorrection/18259199-17332931, http://linkedlifedata.com/resource/pubmed/commentcorrection/18259199-17350670, http://linkedlifedata.com/resource/pubmed/commentcorrection/18259199-7724580, http://linkedlifedata.com/resource/pubmed/commentcorrection/18259199-9230442, http://linkedlifedata.com/resource/pubmed/commentcorrection/18259199-9916986, http://linkedlifedata.com/resource/pubmed/commentcorrection/18259199-9916987
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1350-9047
pubmed:author
pubmed:issnType
Print
pubmed:volume
15
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
831-40
pubmed:dateRevised
2011-3-8
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
X-linked inhibitor of apoptosis deficiency in the TRAMP mouse prostate cancer model.
pubmed:affiliation
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109-2200, USA.
pubmed:publicationType
Journal Article
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