Linked Life Data

17006756

Source:http://linkedlifedata.com/resource/pubmed/id/17006756

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2007-1-24
pubmed:abstractText
Serine/threonine kinase Akt/PKB is known to regulate divergent cellular processes, including apoptosis, proliferation, differentiation, and metabolism. Akt is activated by a variety of stimuli, through such growth factor receptors as HER2, in phosphoinositide-3-OH kinase (PI3K)-dependent manner. A loss of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) function also activates Akt. It has recently been shown that Akt activation is associated with a worse outcome among endocrine treated breast cancer patients and that it also inhibits the progesterone receptor (PR) expression via the PI3K/Akt pathway in breast cancer cells. Therefore, the PI3K/Akt signaling pathway has recently attracted considerable attention as a new target for effective therapeutic strategies. In the present study, we investigated the relationship between Akt activation and either HER2 overexpression or PTEN gene alteration, as well as the PR expression. We analyzed the incidence of LOH at the PTEN locus in 138 breast cancer patients, using our new system for microsatellite analysis, called high-resolution fluorescent microsatellite analysis (HRFMA). We showed Akt activation to significantly correlate with HER2 overexpression or LOH at the PTEN gene locus while inversely correlating with the PR expression. In addition, when LOH at the PTEN gene locus and HER2 overexpression occurred simultaneously, the incidence of Akt activation and reduced PR expression was significant. The association between Akt activation and PR negative expression was observed even in the ER-positive cases. Our results suggest that simultaneous PTEN LOH and HER2 overexpression enhances Akt activation and may thus lead to a negative PR expression.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0167-6806
pubmed:author
pubmed:issnType
Print
pubmed:volume
101
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
249-57
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:17006756-Breast Neoplasms, pubmed-meshheading:17006756-Carcinoma, pubmed-meshheading:17006756-Enzyme Activation, pubmed-meshheading:17006756-Gene Expression Regulation, Neoplastic, pubmed-meshheading:17006756-Humans, pubmed-meshheading:17006756-Loss of Heterozygosity, pubmed-meshheading:17006756-Lymphatic Metastasis, pubmed-meshheading:17006756-Neoplasm Staging, pubmed-meshheading:17006756-PTEN Phosphohydrolase, pubmed-meshheading:17006756-Phosphatidylinositol 3-Kinases, pubmed-meshheading:17006756-Phosphorylation, pubmed-meshheading:17006756-Protein-Serine-Threonine Kinases, pubmed-meshheading:17006756-Proto-Oncogene Proteins c-akt, pubmed-meshheading:17006756-Receptor, erbB-2, pubmed-meshheading:17006756-Receptors, Estrogen, pubmed-meshheading:17006756-Receptors, Progesterone, pubmed-meshheading:17006756-Retrospective Studies, pubmed-meshheading:17006756-Signal Transduction
pubmed:year
2007
pubmed:articleTitle
Coexistence of the loss of heterozygosity at the PTEN locus and HER2 overexpression enhances the Akt activity thus leading to a negative progesterone receptor expression in breast carcinoma.
pubmed:affiliation
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Fukuoka 812-8582, Japan. eriko@surg2.med.kyuhsu-u.ac.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't