Genomic structure of human alpha-pix, and variable deletions in a poly (T)tract in gastric cancer tissue

PAK-interacting exchange factor (PIX) has been reported to mediate the recr uitment of PAK into focal adhesions and activate Rac, thus creating a feedb ack loop that stimulate PAK and other targets. This pathway is thought to b e related to cellular changes, such as transformation and migration, that a re often encountered in cancer cells. Here, we report the genomic structure of alpha-PIX, one of the PAK- interacting exchange factors, including the identification of the promoter region, which consisted 772 amino acids in 2 2 exons, spanning about 100 kb on genome of X chromosome. All splice sites conformed to the GT-AT rule. To investigate the role of alpha-PIX in carcin ogenesis, we screened 60 cases of gastric cancer for mutations and polymorp hisms using an intron-primer that covered all the exons, bur no mutations o r polymorphisms were found in the coding region. However an 18 bp repeat of thymidine tract was present in 50 bp downstream from exon L2 and the delet ion of variable numbers of mononucleotide repeats was observed in seven out of the 60 gastric cancer tissue specimens that were examined. These seven cases all exhibited a mutator phenotype, suggesting that the deletions are passenger mutations. Thus our results revealed that alpha-PIX probably does not play any primary role in human gastric carcinogenesis. (C) 2001 Elsevi er Science Ireland Ltd. All rights: reserved.