KESINEE GATPHAYAK1,3, CHRISTOPH KNORR3, NATTAPHON CHONGKASIKIT1, THERDCHAI VEARASILP1, UDO TER MEULEN2, BERTRAM BRENIG3
1Chiang Mai University, Department of Animal Science, Thailand
2Georg-August-Universität Göttingen, Institute of Animal Physiology and Nutrition, Germany
3Georg-August-Universität Göttingen, Institute of Veterinary Medicine (IVM), Germany
FUS1 is a candidate tumor suppressor gene (TSG) organised in a 370-kb region, which contains a set of 19 genes. The human FUS1 genomic sequence spans 3.3 kb containing three exons. Overexpression of the FUS1 gene leads to G1 arrest and growth inhibition of lung cancer cells, and reduces also the spread of lung cancer in mice. Thus, this gene may provide a novel way of selectively destroying cancer cells in mammals. The human and the murine FUS1 genes were assigned to chromosome HSA3p21.3 and MMU9F1, respectively. Our sequence characterisation of the porcine PAC clone TAIGP714O11196 revealed the identical gene cluster for pigs and humans with respect to genes FUS1, FUS2 and the genes of the HYAL cluster (HYAL1, HYAL2, and HYAL3). We have recently mapped the porcine FUS1 gene to SSC13q21-q22 and reported its localisation upstream of the porcine hyaluronidase gene cluster. Sequencing of the porcine PAC clone led so far to the determination of 3110 bp of genomic FUS1 sequence. This partial sequence contains exons 2 and 3 sharing about 86% and 84% homology with the human cDNA sequence, respectively. We also managed to characterise the 3'-end completely by applying RACE-PCR and cDNA extracted from porcine testis. We further intend to accomplish the complete porcine FUS1 sequence by primer walking to close existing gaps on the clone. In addition, cDNA sequences will be generated to characterise the gene structure and expression analysis will be performed using several different porcine tissues. Finally, screening for polymorphisms in the gene will be done using European, Chinese and Thai native pigs. Possible mutations in the porcine FUS1 gene could make it an attractive candidate for further functional tumor suppressor gene studies and the pig a model animal in cancer research and therapy.
Keywords: FUS1, pig, porcine lung cancer candidate gene