High expression of focal adhesion kinase (p125FAK) in node-negative breast cancer is related to overexpression of HER-2/neu and activated Akt kinase but does not predict outcome

Focal adhesion kinase (FAK) regulates multiple cellular processes including growth, differentiation, adhesion, motility and apoptosis. In breast carcinoma, FAK overexpression has been linked to cancer progression but the prognostic relevance remains unknown. In particular, with regard to lymph node-...

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Published in:Breast cancer research : BCR 2005-01, Vol.7 (2), p.R194-R203, Article R194
Main Authors: Schmitz, Klaus Jürgen, Grabellus, Florian, Callies, Rainer, Otterbach, Friedrich, Wohlschlaeger, Jeremias, Levkau, Bodo, Kimmig, Rainer, Schmid, Kurt Werner, Baba, Hideo Andreas
Format: Article
Language:English
Subjects:
Blotting, Western
Breast Neoplasms - genetics
Breast Neoplasms - pathology
Breast Neoplasms - therapy
Female
Focal Adhesion Kinase 1 - biosynthesis
Gene Expression Profiling
Humans
Immunohistochemistry
Lymphatic Metastasis
Middle Aged
Mitogen-Activated Protein Kinase 1 - metabolism
Mitogen-Activated Protein Kinase 3 - metabolism
Oncogene Protein v-akt - metabolism
Predictive Value of Tests
Prognosis
Receptor, ErbB-2 - physiology
Risk Assessment
Signal Transduction
Treatment Outcome
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Summary:Focal adhesion kinase (FAK) regulates multiple cellular processes including growth, differentiation, adhesion, motility and apoptosis. In breast carcinoma, FAK overexpression has been linked to cancer progression but the prognostic relevance remains unknown. In particular, with regard to lymph node-negative breast cancer it is important to identify high-risk patients who would benefit from further adjuvant therapy. We analyzed 162 node-negative breast cancer cases to determine the prognostic relevance of FAK expression, and we investigated the relationship of FAK with major associated signaling pathways (HER2, Src, Akt and extracellular regulated kinases) by immunohistochemistry and western blot analysis. Elevated FAK expression did not predict patient outcome, in contrast to tumor grading (P = 0.005), Akt activation (P = 0.0383) and estrogen receptor status (P = 0.0033). Significant positive correlations were observed between elevated FAK expression and HER2 overexpression (P = 0.001), as well as phospho-Src Tyr-215 (P = 0.021) and phospho-Akt (P < 0.001), but not with phospho-ERK1/2 (P = 0.108). Western blot analysis showed a significant correlation of FAK Tyr-861 activation and HER2 overexpression (P = 0.01). Immunohistochemical detection of FAK expression is of no prognostic significance in node-negative breast cancer but provides evidence that HER2 is involved in tumor malignancy and metastatic ability of breast cancer through a novel signaling pathway participating FAK and Src.
ISSN:1465-542X
1465-5411
1465-542X
DOI:10.1186/bcr977