Source:http://linkedlifedata.com/resource/pubmed/id/15183529
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
2004-6-8
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pubmed:abstractText |
The enhancement of cell proliferation and promotion of cell survival via the inhibition of apoptosis is thought to be the key to the initiation and progression of cancers. The phosphatidylinositol-3 kinase (PI3K)/Akt is an important survival signal pathway that has been shown to be crucial in the regulation of balance between pro-apoptotic and survival (anti-apoptotic) signal. In this study, the expression of phosphorylated Akt at Thr308 and Ser473, BCL-2-antagonist of cell death (BAD) at Ser136 and glycogen synthase kinase-3beta (GSK-3beta) at Ser9 in 47 paraffin-embedded human colorectal carcinoma (CRC) tissues were determined by immunohistochemical staining in order to dissect the alterations in the signal transduction pathways in CRC. Our results showed that there was a significant increase in the expression of these biomolecules in CRC tissues compared to the apparently normal adjacent tissues. The frequency of increased expression in tumor colonic mucosa were as follows: p-Akt1/2/3 (Thr308) = 16/47 (34%); p-Akt1 (Ser473) = 21/47 (44.7%); phospho-BAD (p-BAD) Ser136 = 27/47 (57.4%) and phospho-GSK-3beta (p-GSK-3beta) = 21/47 (44.7%). Analysis of the total p-Akt1 (Ser473), p-Akt1/2/3 (Thr308), p-GSK-3beta (Ser9) and p-BAD (Ser136) score found that there was a statistically significant relationship with each other. A statistically significant positive linear relationship was found between total p-Akt (Ser473) score and total p-GSK-3beta (Ser9) score as well as with total p-BAD (Ser136) score. On the other hand, total p-Akt1/2/3 (Thr308) scores had a statistically significant positive linear relationship with p-GSK-3beta (Ser9) only. The Akt targets, p-GSK-3beta (Ser9) and p-BAD (Ser136) were positively correlated to each other. There was no significant correlation between clinico-pathological data with total p-Akt1 (Ser473), p-Akt1/2/3 (Thr308), p-GSK-3beta (Ser9) and p-BAD (Ser136) score except for age. The total scores of p-GSK-3beta were found to be higher in patients in the age group of greater than 60. This is the first report of p-Akt1/2/3 (Thr308) and p-BAD (Ser136) expression in primary colorectal tumor tissue. Our data further supports the role of PI3K/Akt signaling pathways in the pathogenesis of CRC and contributes to the identification of target molecules in the signal transduction pathway for cancer therapy.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/AKT1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Glycogen Synthase Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2,
http://linkedlifedata.com/resource/pubmed/chemical/Serine,
http://linkedlifedata.com/resource/pubmed/chemical/Threonine,
http://linkedlifedata.com/resource/pubmed/chemical/glycogen synthase kinase 3 beta
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0304-3835
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pubmed:author | |
pubmed:copyrightInfo |
Copyright 2004 Elsevier Ireland Ltd.
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pubmed:issnType |
Print
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pubmed:day |
16
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pubmed:volume |
210
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
139-50
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pubmed:dateRevised |
2011-11-2
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pubmed:meshHeading |
pubmed-meshheading:15183529-Age Factors,
pubmed-meshheading:15183529-Aged,
pubmed-meshheading:15183529-Apoptosis,
pubmed-meshheading:15183529-Colorectal Neoplasms,
pubmed-meshheading:15183529-Female,
pubmed-meshheading:15183529-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:15183529-Glycogen Synthase Kinase 3,
pubmed-meshheading:15183529-Humans,
pubmed-meshheading:15183529-Immunohistochemistry,
pubmed-meshheading:15183529-Male,
pubmed-meshheading:15183529-Middle Aged,
pubmed-meshheading:15183529-Phosphorylation,
pubmed-meshheading:15183529-Protein-Serine-Threonine Kinases,
pubmed-meshheading:15183529-Proto-Oncogene Proteins,
pubmed-meshheading:15183529-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:15183529-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:15183529-Serine,
pubmed-meshheading:15183529-Signal Transduction,
pubmed-meshheading:15183529-Threonine,
pubmed-meshheading:15183529-Tumor Cells, Cultured,
pubmed-meshheading:15183529-Up-Regulation
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pubmed:year |
2004
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pubmed:articleTitle |
Positive correlation between overexpression of phospho-BAD with phosphorylated Akt at serine 473 but not threonine 308 in colorectal carcinoma.
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pubmed:affiliation |
Department of Clinical Laboratory Sciences, Faculty of Medicine and Health Science, Universiti Putra Malaysia, Serdang, Selangor 43400, Malaysia.
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pubmed:publicationType |
Journal Article,
Comparative Study
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