Impaired RNA splicing of 5'-regulatory sequences of the astroglial glutamate transporter EAAT2 in human astrocytoma

A loss of the glutamate transporter EAAT2 has been reported in the neoplastic transformation of astrocytic cells and astrocytoma. The RNA expression of EAAT2 and five 5'-regulatory splice variants was investigated to identify alterations of the post-transcriptional EAAT2 gene regulation in human astrocytic tumours.
Three known (EAAT2, HBGTII, and HBGTIIC) and two novel (EAAT2/3 and EAAT2/31) EAAT2 transcripts originating from alternative splicing of 5'-regulatory sequences were subject to an RNA expression analysis using reverse transcription and competitive PCR. Specimens of astrocytoma World Health Organisation (WHO) grade I-IV in 14patients and control brain tissue obtained from three normal persons were studied.
The main EAAT2 RNA was found to be equally expressed in normal human brain and astrocytic tumour samples. By contrast, the expression pattern of four 5'-variants of the transporter transcript was altered in the investigated series of astrocytoma compared with normal brain. HBGTII, HBGTIIC, and EAAT2/3 were amplified from seven and four tumours and one sample, respectively. EAAT2/31 was expressed in none of the tumour specimens studied.
In conclusion, in astrocytic tumours of different histopathological grades there was a substantial reduction of RNA splicing events in EAAT2. The impairment of EAAT2 splicing indicates an altered expression which is not primarily involved in the tumorigenesis but may contribute to some biological properties of astrocytoma such as oedema, necrosis, and tumour related seizures.


Abstract Ž. Thin Solid Films 387 2001 165�168 Optimisation

The special features of the CISCuT material require cell concepts that differ from conventional CuInS2 solar cells. For the n-type CISCuT bulk material, a p-type buffer is required. In this paper, the currently used p-type CuŽ O,S. buffer layer is replaced 2 by the higher bandgap material CuI. On 10-mm cells the efficiency profit made by the replacement of CuŽ O,S. with CuI is demonstrated. For larger cell areas, two different cell configurations are described. In the first concept, a ZnO:Al window layer is deposited on top of the CuI buffer layer. The second concept uses a metal grid as a front contact. Theoretical considerations point out the consequences of the given concepts for the CISCuT cell performance. For the Cu�CISCuT�CuI�ZnO:Al layer configuration, an additional tunnel junction is expected at the interface between the p-type CuI and the n-type ZnO:Al. In the metal grid concept, CuI doping with iodine is required to lower the sheet resistance of the layer. Some precautions against iodine out-diffusion have to be taken. For the window layer configuration on an area of 400 mm2, a cell performance of 5.2 % wa