Expression of EAG potasssium channels in tumor tissue

LA Pardo, MD, PhD a, b,B. Hemmerlein, MD c, A. Sánchez, MD b, H.J. Radzun, MD c, W. Stühmer, PhD b

a iOnGen AG, Goettingen, Germany b Max-Planck-Insitute for Experimental Medicine, Göttingen, Germany c Department of Pathology, University Hospital Göttingen, Germany

AIM EAG1 potassium channels have been described to show oncogenic properties. Cells overexpressing EAG1 exhibit a transformed phenotype, and tumor progression in vivo is favored by expression of the channel. Several tumor cell lines show aberrant EAG1 expression and inhibition of the channel mRNA reduces growth of these cells.1 METHODS We have generated monoclonal anti-EAG1 antibodies to determine the distribution pattern of the protein both in normal and neoplastic human tissues in combination with real-time PCR. RESULTS We concentrated on primary breast carcinomas, because we had found the channel in ductal carcinoma-derived cell lines. While normal breast tissue is not stained with our antibodies, over 90% of the tumors tested showed strongly positive staining. The ectopic expression of EAG in many tumor tissues was confirmed by RT-PCR. Not only mammary carcinoma was found to be positive for EAG, but also other solid tumors showed clearly positive signals at very high frequency. Lung, prostate, colon and liver carcinoma are positive in more than 90% of the cases studied. CONCLUSIONS EAG is a very widely distributed tumor marker. It offers the possibility for the design of a new therapeutic approach, since it seems to be required for tumor cell growth, and it is accessible from the outside in intact cells, apparently present in very low amounts in normal cells although abundant in tumor cells, and its normal location is protected by the blood-brain barrier.

KEY WORDS: ion channels, immunohistochemistry, tumor markers, therapy targets.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Novel Therapies, Part 2.