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Background: Lipoic acid synthetase (LIAS) gene encode for a protein that belongs to the biotin and lipoic acid synthetases family. It is localized at chromosome 4p14 and is alternative spliced resulting in two transcript variants. Variant two lacks an alternately spliced exon 8 resulting in a shorter transcript. Gene product localizes in mitochondrion and plays an important role in alpha-(+)-lipoic acid synthesis. Alpha-lipoic acid induced apoptosis in a number of human tumour cell lines by the mechanism independent of Fas-mediated signalling which raised an interest in investigating the expression pattern of this gene in lung cancer. Aim: The main aim of this study was to investigate the expression pattern of LIAS in human lung cancers. Materials and Methods: LIAS expression level was investigated using in situ hybridization on wax embedded tissue sections for the normal lung and lung cancer (small cell carcinoma, adernocarcinoma, large cell carcinoma and squaomous cell carcinoma). To confirm the expression level, Quantitative RT-PCR was used. RNA probes complementary to the two LIAS mRNA transcripts were synthesized, labelled with Digoxigenin and used to investigate the expression of LIAS mRNA in the normal and cancer tissue sections. Results: In situ hybridization and quantitative RT-PCR results showed down-regulation of LIAS in lung cancer as compared to the normal. The expression pattern of this gene in lung cancer pathologies showed a higher expression in adernocarcinoma, followed by squamous cell lung carcinoma, small cell lung carcinoma and the least in large cell lung carcinoma. Variant 1 was found to be more expressed than variant 2 in both the normal and cancerous state. Conclusion: The down-regulation of LIAS in cancer cells suggests that this gene possibly have a direct or indirect effect to the response of cells to apoptosis. Thus determination of LIAS mRNA expression in cancer tissues can serve as the preliminary step to future studies that will elucidate the role of LIAS in the development of cancer.

[Proc Amer Assoc Cancer Res, Volume 47, 2006]