Cytosolic phospholipase A2-alpha expression in breast cancer is associated with EGFR expression and correlates with an adverse prognosis in luminal tumours.

Hdl Handle:
http://hdl.handle.net/10147/207209
Title:
Cytosolic phospholipase A2-alpha expression in breast cancer is associated with EGFR expression and correlates with an adverse prognosis in luminal tumours.
Authors:
Caiazza, F; McCarthy, N S; Young, L; Hill, A D K; Harvey, B J; Thomas, W
Affiliation:
Department of Molecular Medicine, Royal College of Surgeons in Ireland, Education, and Research Centre, Beaumont Hospital, Dublin 9, Ireland.
Citation:
Br J Cancer. 2011 Jan 18;104(2):338-44. Epub 2010 Nov 30.
Journal:
British journal of cancer
Issue Date:
1-Feb-2012
URI:
http://hdl.handle.net/10147/207209
DOI:
10.1038/sj.bjc.6606025
PubMed ID:
21119660
Abstract:
BACKGROUND: The eicosanoid signalling pathway promotes the progression of malignancies through the production of proliferative prostaglandins (PGs). Cytosolic phospholipase A(2)alpha (cPLA(2)alpha) activity provides the substrate for cyclooxygenase-dependent PG release, and we have previously found that cPLA(2)alpha expression correlated with EGFR/HER2 over-expression in a small number of breast cancer cell lines. METHODS: The importance of differential cPLA(2)alpha activity in clinical breast cancer was established by relating the expression of cPLA(2)alpha in tissue samples from breast cancer patients, and two microarray-based gene expression datasets to different clinicopathological and therapeutic parameters. RESULTS: High cPLA(2)alpha mRNA expression correlated with clinical parameters of poor prognosis, which are characteristic of highly invasive tumours of the HER2-positive and basal-like subtype, including low oestrogen receptor expression and high EGFR expression. High cPLA(2)alpha expression decreased overall survival in patients with luminal cancers, and correlated with a reduced effect of tamoxifen treatment. The cPLA(2)alpha expression was an independent predictive parameter of poor response to endocrine therapy in the first 5 years of follow-up. CONCLUSION: This study shows a role of cPLA(2)alpha in luminal breast cancer progression, in which the enzyme could represent a novel therapeutic target and a predictive marker.
Language:
eng
MeSH:
Antineoplastic Agents, Hormonal/therapeutic use; Breast Neoplasms/drug therapy/*enzymology/pathology; Cohort Studies; Cytosol/*enzymology; Female; Humans; Oligonucleotide Array Sequence Analysis; Phospholipases A2/genetics/*metabolism; Prognosis; RNA, Messenger/genetics; Receptor, Epidermal Growth Factor/*metabolism; Reverse Transcriptase Polymerase Chain Reaction
ISSN:
1532-1827 (Electronic); 0007-0920 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorCaiazza, Fen_GB
dc.contributor.authorMcCarthy, N Sen_GB
dc.contributor.authorYoung, Len_GB
dc.contributor.authorHill, A D Ken_GB
dc.contributor.authorHarvey, B Jen_GB
dc.contributor.authorThomas, Wen_GB
dc.date.accessioned2012-02-01T10:02:00Z-
dc.date.available2012-02-01T10:02:00Z-
dc.date.issued2012-02-01T10:02:00Z-
dc.identifier.citationBr J Cancer. 2011 Jan 18;104(2):338-44. Epub 2010 Nov 30.en_GB
dc.identifier.issn1532-1827 (Electronic)en_GB
dc.identifier.issn0007-0920 (Linking)en_GB
dc.identifier.pmid21119660en_GB
dc.identifier.doi10.1038/sj.bjc.6606025en_GB
dc.identifier.urihttp://hdl.handle.net/10147/207209-
dc.description.abstractBACKGROUND: The eicosanoid signalling pathway promotes the progression of malignancies through the production of proliferative prostaglandins (PGs). Cytosolic phospholipase A(2)alpha (cPLA(2)alpha) activity provides the substrate for cyclooxygenase-dependent PG release, and we have previously found that cPLA(2)alpha expression correlated with EGFR/HER2 over-expression in a small number of breast cancer cell lines. METHODS: The importance of differential cPLA(2)alpha activity in clinical breast cancer was established by relating the expression of cPLA(2)alpha in tissue samples from breast cancer patients, and two microarray-based gene expression datasets to different clinicopathological and therapeutic parameters. RESULTS: High cPLA(2)alpha mRNA expression correlated with clinical parameters of poor prognosis, which are characteristic of highly invasive tumours of the HER2-positive and basal-like subtype, including low oestrogen receptor expression and high EGFR expression. High cPLA(2)alpha expression decreased overall survival in patients with luminal cancers, and correlated with a reduced effect of tamoxifen treatment. The cPLA(2)alpha expression was an independent predictive parameter of poor response to endocrine therapy in the first 5 years of follow-up. CONCLUSION: This study shows a role of cPLA(2)alpha in luminal breast cancer progression, in which the enzyme could represent a novel therapeutic target and a predictive marker.en_GB
dc.language.isoengen_GB
dc.subject.meshAntineoplastic Agents, Hormonal/therapeutic useen_GB
dc.subject.meshBreast Neoplasms/drug therapy/*enzymology/pathologyen_GB
dc.subject.meshCohort Studiesen_GB
dc.subject.meshCytosol/*enzymologyen_GB
dc.subject.meshFemaleen_GB
dc.subject.meshHumansen_GB
dc.subject.meshOligonucleotide Array Sequence Analysisen_GB
dc.subject.meshPhospholipases A2/genetics/*metabolismen_GB
dc.subject.meshPrognosisen_GB
dc.subject.meshRNA, Messenger/geneticsen_GB
dc.subject.meshReceptor, Epidermal Growth Factor/*metabolismen_GB
dc.subject.meshReverse Transcriptase Polymerase Chain Reactionen_GB
dc.titleCytosolic phospholipase A2-alpha expression in breast cancer is associated with EGFR expression and correlates with an adverse prognosis in luminal tumours.en_GB
dc.contributor.departmentDepartment of Molecular Medicine, Royal College of Surgeons in Ireland, Education, and Research Centre, Beaumont Hospital, Dublin 9, Ireland.en_GB
dc.identifier.journalBritish journal of canceren_GB
dc.description.provinceLeinster-

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