Signalling networks associated with urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 in breast cancer tissues: new insights from protein microarray analysis |
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Authors: | Wolff Claudia Malinowsky Katharina Berg Daniela Schragner Kerstin Schuster Tibor Walch Axel Bronger Holger Höfler Heinz Becker Karl-Friedrich |
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Affiliation: | 1. Institute of Pathology, Technische Universit?t München, Munich, Germany;2. Institute of Medical Statistics and Epidemiology, Technische Universit?t München, Munich, Germany;3. Institute of Pathology, Helmholtz Zentrum München, German Research Centre for Environmental Health, Neuherberg, Germany;4. Institute of Obstetrics and Gynaecology, Technische Universit?t München, Munich, Germany |
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Abstract: | The urokinase-type plasminogen activator (uPA) and the main uPA inhibitor PAI-1 play important roles in cell migration and invasion in both physiological and pathological contexts. Both factors are clinically applicable predictive markers in node-negative breast cancer patients that are used to stratify patients for adjuvant chemotherapy. In addition to their classical functions in plasmin regulation, both factors are key components in cancer-related cell signalling. Such signalling cascades are well described in cell culture systems, but a better understanding of uPA- and PAI-1-associated signalling networks in clinical tissues is needed. We examined the expression of uPA, PAI-1, and 21 signalling molecules in 201 primary breast cancer tissues using protein microarrays. Expression of uPA was significantly correlated with the expression of ERK and Stat3, while expression of PAI-1 was correlated with the uPA receptor and Akt activation, presumably via integrin and HER-receptor signalling. Analysis of uPA expression did not reveal any significant correlation with staging, grading or age of the patients. The PAI-1 expression was correlated with nodal stage. Network monitoring for uPA and PAI-1 in breast cancer reveals interactions with main signalling cascades and extends the findings from cell culture experiments. Our results reveal possible mechanisms underlying cancer development. |
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Keywords: | urokinase‐type plasminogen activator (uPA) plasminogen activator inhibitor 1 (PAI‐1) migration invasion formalin‐fixed paraffin‐embedded tissue (FFPE) cell signalling protein microarray reverse phase protein microarray |
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