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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.
Breast Cancer Res. 2005; 7(2):R194-203.BC

Abstract

INTRODUCTION

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.

METHODS

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.

RESULTS

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).

CONCLUSIONS

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.

Authors+Show Affiliations

Institute of Pathology, University Hospital of Essen-Duisburg, Essen, Germany. klaus.schmitz@uni-essen.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15743500

Citation

Schmitz, Klaus Jürgen, et al. "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." Breast Cancer Research : BCR, vol. 7, no. 2, 2005, pp. R194-203.
Schmitz KJ, Grabellus F, Callies R, et al. 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. Breast Cancer Res. 2005;7(2):R194-203.
Schmitz, K. J., Grabellus, F., Callies, R., Otterbach, F., Wohlschlaeger, J., Levkau, B., Kimmig, R., Schmid, K. W., & Baba, H. A. (2005). 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. Breast Cancer Research : BCR, 7(2), R194-203.
Schmitz KJ, et al. 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. Breast Cancer Res. 2005;7(2):R194-203. PubMed PMID: 15743500.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Schmitz,Klaus Jürgen, AU - Grabellus,Florian, AU - Callies,Rainer, AU - Otterbach,Friedrich, AU - Wohlschlaeger,Jeremias, AU - Levkau,Bodo, AU - Kimmig,Rainer, AU - Schmid,Kurt Werner, AU - Baba,Hideo Andreas, Y1 - 2005/01/07/ PY - 2004/08/17/received PY - 2004/11/22/revised PY - 2004/11/26/accepted PY - 2005/3/4/pubmed PY - 2006/2/1/medline PY - 2005/3/4/entrez SP - R194 EP - 203 JF - Breast cancer research : BCR JO - Breast Cancer Res VL - 7 IS - 2 N2 - INTRODUCTION: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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. SN - 1465-542X UR - https://www.unboundmedicine.com/medline/citation/15743500/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_ L2 - https://breast-cancer-research.biomedcentral.com/articles/10.1186/bcr977 DB - PRIME DP - Unbound Medicine ER -