Linked Life Data

15307142

Source:http://linkedlifedata.com/resource/pubmed/id/15307142

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2004-8-12
pubmed:abstractText
PTEN is a novel tumour suppressor gene located on chromosome 10. PTEN mutations are believed to exert their effects through the putative PI3K-AKT-mTOR signalling pathway. Specifically, loss of PTEN leads to activation of AKT, which in turn promotes anti-apoptotic and pro-cell cycle entry pathways believed to be essential in tumourigenesis. Whilst PTEN mutations are frequent in a variety of sporadic cancers and inherited cancer syndromes, it is not clear how frequently PTEN mutations and immunohistochemical loss of PTEN expression occur in sporadic breast cancer. This study used tissue microarrays (TMAs) to assess wild-type PTEN and pAKT immunohistochemical staining in 670 and 691 cases, respectively, of primary operable breast cancer. Scores of 0, 1, and 2 were given for negative, weakly positive, and strongly positive degrees of immunoreactivity, respectively. In addition, immunohistochemical assessment of epidermal growth factor receptor (EGFR), Her2, and proliferation by MIB1 expression was performed on the same TMAs and the scores were compared with those of PTEN and pAKT. Eight per cent of cases did not express wild-type PTEN. No correlation was observed between patient, tumour and outcome variables and PTEN. pAKT expression correlated inversely with adverse tumour variables such as tumour grade (p< 0.001) and correlated positively with ER status (p< 0.001). No correlation was seen between either PTEN or AKT and EGFR, Her2 or MIB1. No association of PTEN or pAKT was seen in Kaplan-Meier or multivariate analysis for overall survival. The results indicate that loss of PTEN expression is infrequent in breast cancer. PTEN and AKT do not appear to be prognostic markers. The study argues against the current model of a simple linear tumourigenic PTEN-PI3K-AKT-mTOR pathway in breast cancer. It also suggests that, in this group of breast cancers, the most common upstream regulator of AKT may be ER rather than PTEN, EGFR or Her2.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0022-3417
pubmed:author
pubmed:copyrightInfo
Copyright 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
pubmed:issnType
Print
pubmed:volume
204
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
93-100
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:15307142-Adult, pubmed-meshheading:15307142-Aged, pubmed-meshheading:15307142-Breast Neoplasms, pubmed-meshheading:15307142-Cell Transformation, Neoplastic, pubmed-meshheading:15307142-Female, pubmed-meshheading:15307142-Humans, pubmed-meshheading:15307142-Immunoenzyme Techniques, pubmed-meshheading:15307142-Middle Aged, pubmed-meshheading:15307142-Neoplasm Proteins, pubmed-meshheading:15307142-PTEN Phosphohydrolase, pubmed-meshheading:15307142-Phosphoric Monoester Hydrolases, pubmed-meshheading:15307142-Prognosis, pubmed-meshheading:15307142-Protein-Serine-Threonine Kinases, pubmed-meshheading:15307142-Proto-Oncogene Proteins, pubmed-meshheading:15307142-Proto-Oncogene Proteins c-akt, pubmed-meshheading:15307142-Signal Transduction, pubmed-meshheading:15307142-Survival Analysis, pubmed-meshheading:15307142-Tumor Markers, Biological, pubmed-meshheading:15307142-Tumor Suppressor Proteins
pubmed:year
2004
pubmed:articleTitle
The role of PTEN and its signalling pathways, including AKT, in breast cancer; an assessment of relationships with other prognostic factors and with outcome.
pubmed:affiliation
Department of Histopathology, Nottingham Breast Unit, Nottingham City Hospital, Nottingham, UK.
pubmed:publicationType
Journal Article