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 recruitment of PAK into focal adhesions and activate Rac, thus creating a feedback loop that stimulate PAK and other targets. This pathway is thought to be related to cellular changes, such as transformation and migration, that are 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 22 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 carcinogenesis, we screened 60 cases of gastric cancer for mutations and polymorphisms using an intron-primer that covered all the exons, but no mutations or polymorphisms were found in the coding region. However an 18 bp repeat of thymidine tract was present in 50 bp downstream from exon 12 and the deletion 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.
Wang
Y J
YJ
First Department of Pathology, Hamamatsu University, School of Medicine, 3600 Handa-cho, Hamamatsu 431-3192, Japan.
Oba
S M
SM
Yoshii
S
S
Song
J P
JP
Wang
Y
Y
Kanamori
M
M
Ota
S
S
Tanaka
M
M
Sugimura
H
H
D000483:Alleles; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000235:genetics*; D003001:Cloning, Molecular; D005091:Exons; D017353:Gene Deletion; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics*; D006801:Humans; D007438:Introns; D018895:Microsatellite Repeats; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D011071:Poly T / Q000235:genetics*; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D011401:Promoter Regions, Genetic; D064067:Rho Guanine Nucleotide Exchange Factors; D017422:Sequence Analysis, DNA; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism*; D014960:X Chromosome
D018797:Cell Cycle Proteins; D020662:Guanine Nucleotide Exchange Factors; D064067:Rho Guanine Nucleotide Exchange Factors; D011071:Poly T