gms | German Medical Science

Objective: Kv10.1, a voltage gated potassium channel is natively expressed in the brain, where it likely participates in control of cell excitability. Additionally, it is implicated in malignant transformation and tumor progression in many cancer cell lines and human malignancies. Previous few reports about the expression of Kv10.1 mRNA in gliomas provide controversial observations depending on the malignancy grade and tumor lineage. Data about brain metastases are lacking.

Methods: We have analyzed 3 brain metastases of breast- and oesophagus carcinoma as well as melanoma, 6 glioblastomas and 1 oligodendroglioma WHO grade II. For this purpose nested PCR and RT-PCR were performed. Furthermore nested PCR products have been cloned and verified by direct sequencing. Functional properties were examined by electrophysiological measurements of co-transfected wild type and splice variant ion channel.

Results: By RT PCR, 5 out of 6 glioblastomas, 2 of 3 brain metastases and the oligodendroglioma were positive for wild-type KV10.1 mRNA. A Sequence analysis of the verified clones showed the presence of a sequence coding for the wild-type KV10.1 ion channel but also the presence of a novel splice variant only in brain metastases. Evaluation of the novel splice variant showed that the sequence coding for the transmembrane domains, termed S1–S6, is missing.

Conclusions: We report on the identification and characterization in brain metastases of a KV10.1 potassium channel novel protein as well as the functional properties of this protein which contains the N-and C-terminal sequences but lacks all channel forming transmembrane domains. Our data might open new perspectives to develop novel target therapy strategies in brain metastases.