Overexpression of cyclo-oxygenase-2 is an independent predictor of unfavourable outcome in node-negative breast cancer, but is not associated with protein kinase B (Akt) and mitogen-activated protein kinase (ERK1/2, p38) activation or with Her-2/neu signalling pathways

Background and aim: The production of prostaglandins is regulated by cyclo-oxygenases (COXs), which also have a role in tumour development and progression in various malignancies, including breast cancer. The mechanisms by which COX-2 contributes to unfavourable prognosis are still poorly understood...

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Bibliographic Details
Published in:Journal of clinical pathology 2006-07, Vol.59 (7), p.685-691
Main Authors: Schmitz, K J, Callies, R, Wohlschlaeger, J, Kimmig, R, Otterbach, F, Bohr, J, Lee, H-S, Takeda, A, Schmid, K W, Baba, H A
Format: Article
Language:English
Subjects:
Aged
Biomarkers, Tumor - metabolism
Breast cancer
Breast Neoplasms - enzymology
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
COX
cyclo-oxygenase
Cyclooxygenase 2 - metabolism
ERK
extracellular regulated kinases
familial adenomatous polyposis
FAP
Female
FISH
fluorescent in situ hybridisation
Follow-Up Studies
Genotype & phenotype
Growth factors
Humans
IHC
Immunoglobulins
immunohistochemistry
In Situ Hybridization, Fluorescence
Kinases
Lymphatic system
MAPK
Medical prognosis
Middle Aged
mitogen-activated protein kinase
Neoplasm Proteins - metabolism
non-steroidal anti-inflammatory drug
NSAID
Original
p38 Mitogen-Activated Protein Kinases - metabolism
pAkt
pERK
PGE2
Phosphatase
phospho-Akt
phospho-ERK
phospho-p38
Phosphorylation
pp38
Prognosis
prostaglandin E2
Protein expression
Proteins
Proto-Oncogene Proteins c-akt - metabolism
Receptor, ErbB-2 - metabolism
Signal Transduction
sodium salt citrate
SSC
Statistical analysis
Studies
Survival Analysis
Tumors
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Summary:Background and aim: The production of prostaglandins is regulated by cyclo-oxygenases (COXs), which also have a role in tumour development and progression in various malignancies, including breast cancer. The mechanisms by which COX-2 contributes to unfavourable prognosis are still poorly understood. The association between expression of COX-2 and possible linked signalling pathways—namely, Akt, extracellular regulated kinases (ERK1/2), the stress-activated kinase p38 or Her-2/neu—is assessed in a series of 113 node-negative breast cancers. Results: COX-2 was identified as an independent prognostic factor (p = 0.034) in node-negative breast cancer by survival analysis. The lack of a relationship between COX-2 expression and activated Akt, Erk1/2, p38 and Her-2/neu was indicated by statistical analysis. Conclusions: The prognostic effect of COX-2 expression on lymph node-negative breast cancer is confirmed—COX-2 is probably not regulated by HER-2, Akt, Erk1/2 or p38. Further studies are necessary for the elucidation of the signalling pathways responsible for the modification of COX-2 expression and the increased aggressiveness of breast cancers overexpressing COX-2.
ISSN:0021-9746
1472-4146
DOI:10.1136/jcp.2005.030650