RGD Reference Report - Elevated Src kinase activity attenuates Tamoxifen response in vitro and is associated with poor prognosis clinically. - Rat Genome Database

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Elevated Src kinase activity attenuates Tamoxifen response in vitro and is associated with poor prognosis clinically.

Authors: Morgan, L  Gee, J  Pumford, S  Farrow, L  Finlay, P  Robertson, J  Ellis, I  Kawakatsu, H  Nicholson, R  Hiscox, S 
Citation: Morgan L, etal., Cancer Biol Ther. 2009 Aug;8(16):1550-8.
RGD ID: 2315076
Pubmed: PMID:19830888   (View Abstract at PubMed)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Breast Neoplasms disease_progressionIDA 2315076protein:altered localization:cytoplasmRGD 
Breast Neoplasms disease_progressionISOSRC (Homo sapiens)2315076; 2315076protein:altered localization:cytoplasmRGD 

Objects Annotated

Genes (Rattus norvegicus)
Src  (SRC proto-oncogene, non-receptor tyrosine kinase)

Genes (Mus musculus)
Src  (Rous sarcoma oncogene)

Genes (Homo sapiens)
SRC  (SRC proto-oncogene, non-receptor tyrosine kinase)


Additional Information