Article
Expression of Kv10.1 and KCNN3 potassium ion channels in gliomas
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Published: | May 13, 2014 |
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Objective: The latest research suggests that cellular migration and invasion in cancer cells in general, and glioma cells in particular, are facilitated by ion channels. It has been shown that K+ channels play an important role in migration/invasion, cell cycle progression, cell volume control, and apoptosis. Specifically the Kv10.1 potassium channel is known to be implicated in malignant transformation and tumor progression in many cancer cell lines and tumor tissues. Unfortunately a previous report about mRNA expression of Kv10.1 in gliomas showed controversial results depending on the malignancy grade and histological subtypes. KCNN3 channel is prominently expressed in breast cancer where it promotes cancer cell migration. Up to now KCNN3 transcript has been analyzed only in human tumor cells of astrocytic origin (WHO IV).
Method: In the present work we examine mRNA of two potassium channels; Kv10.1 and KCNN3 in 40 glioma tissues of different malignancy grades (WHO I-IV) and histological subtypes (Astrocytom I, Astrocytom II, Oligoastrocytom II, Oligodendrogliom II, Astrocytom III and Glioblastom). The expression levels were studied by RT-PCR using previously shown suitable reference genes TBP, HMBS and HPRT1. In parallel we examined protein expression of those channels by western blotting.
Results: mRNA of both channels could be detected in all examined tissues. For Kv10.1 channel the decrease of expression level from WHO II to IV was significant (p= 0.0031) as well as from WHO III to IV (p= 0.0067). The highest mRNA expression level was detected in WHO II which could be confirmed by protein analysis. KCNN3 shows the same tendency considering the grading of the tumors and we found a significant change in expression between WHO II and IV (p= 0.0414). The highest mRNA expression level for KCNN3 was again detected in low-grade glioma (WHO II). Interestingly KCNN3 protein was absent from 7 out of 10 GBM analyzed tissues. Protein expression level from tissues sample WHO II and III correlate with mRNA expression.
Conclusions: Our findings strongly suggest a differential expression of Kv10.1 and KCNN3 in gliomas depending on the malignancy grade and nature of the tumor cells, with the highest expression level of both channels in low-grade gliomas. Further examination of these channels in lower tumor grades is important in order to examine their potential role in tumor progression.