Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
16
pubmed:dateCreated
2009-10-14
pubmed:abstractText
Activated Src kinase may contribute to the progression and spread of breast cancers and recent in vitro evidence suggests a role for Src in acquired endocrine resistance. The purpose of this study was to investigate whether modulation of Src activity in endocrine-sensitive and endocrine-resistant breast cancer cells directly affected their phenotype and sensitivity to 4-hydroxy Tamoxifen (tamoxifen) and to determine whether Src activity in breast cancer tissue affected patient outcome. Expression of constitutively active Src in ER-positive, endocrine-sensitive MCF7 breast cancer cells resulted in the development of an aggressive phenotype, akin to that previously observed in cell models of Tamoxifen resistance, and, significantly, attenuated their response to tamoxifen. Conversely, expression of dominant negative-Src in tamoxifen-resistant MCF7 cells resensitized them to tamoxifen. An exploratory immunohistochemical study of an archival primary breast tumor series (n = 75) with parallel clinicopathological data and in normal breast tissues (n = 19) revealed higher levels of activated Src in the cytoplasm (p < 0.01) and lower levels of nuclear Src (p < 0.01) in tumor tissue compared with normal tissue. Whereas elevated levels of activated-Src in the cytoplasm of tumors was significantly associated with reduced survival in ER+ patients (p = 0.031), elevated levels of activated Src within the nucleus appeared to associate with an improved hormonal response. Together these data are further suggestive of a role for Src in breast cancer where it may alter response to endocrine therapy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1555-8576
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1550-8
pubmed:meshHeading
pubmed-meshheading:19830888-Adult, pubmed-meshheading:19830888-Antineoplastic Agents, Hormonal, pubmed-meshheading:19830888-Breast Neoplasms, pubmed-meshheading:19830888-Cell Growth Processes, pubmed-meshheading:19830888-Cell Line, Tumor, pubmed-meshheading:19830888-Drug Resistance, Neoplasm, pubmed-meshheading:19830888-Female, pubmed-meshheading:19830888-Humans, pubmed-meshheading:19830888-Immunohistochemistry, pubmed-meshheading:19830888-Lymphatic Metastasis, pubmed-meshheading:19830888-Middle Aged, pubmed-meshheading:19830888-Neoplasm Recurrence, Local, pubmed-meshheading:19830888-Prognosis, pubmed-meshheading:19830888-Receptors, Estrogen, pubmed-meshheading:19830888-Survival Rate, pubmed-meshheading:19830888-Tamoxifen, pubmed-meshheading:19830888-Tumor Markers, Biological, pubmed-meshheading:19830888-src-Family Kinases
pubmed:year
2009
pubmed:articleTitle
Elevated Src kinase activity attenuates Tamoxifen response in vitro and is associated with poor prognosis clinically.
pubmed:affiliation
Department of Medical Biochemistry & Immunology, Cardiff University, Cardiff, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't