Tissue-specific cancer-related serpin gene cluster at human chromosome band 3q26.
Approximately one quarter of the identified human serpin genes are cancer-related and clustered mainly at two distinct loci: 6p25 and 18q21. We have studied a novel serpin gene cluster at 3q26 containing at least two recently identified members: the pancreas-specific protease inhibitor, pancpin (PI14), and the brain-associated protease inhibitor, neuroserpin (PI12). In this, unlike a previous study, both PI14 and PI12 at 3q26 were found to consist of 9 exons and 8 introns and to share a perfectly conserved gene organization whose pattern is very different from that of the ov-serpin family. This distinct pattern appears identical in the genomic structures of human plasminogen activator inhibitor-1 (PAI1) at 7q21 and protease nexin 1 (PI7) at 2q33-35, confirming that these four genes in three different chromosomes form a discrete subset within the serpin superfamily. As in the other three members whose gene expression is altered during tumorigenesis, PI12 expression was found to be down-regulated in tumor brain tissues and in two brain cancer cell lines: U-87 MG and H4. By screening genomic libraries, we isolated two overlapping clones showing that the marker SGC32223 (centromere) is located within intron F of PI12 and the marker WI-10077 (telomere) is located downstream of the 3'-flanking region of PI14. This finding indicates that the distance between human PI14 and PI12 is approximately 100 kb, and hence we speculate that other tissue-specific cancer-related serpin genes are likely to reside within this 3q26.1 cluster region.
Chang
W S
WS
President's Laboratory, National Health Research Institutes, Taipei, Taiwan.
Chang
N T
NT
Lin
S C
SC
Wu
C W
CW
Wu
F Y
FY
D000595:Amino Acid Sequence; D000818:Animals; D017101:Bacteriophage P1 / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000302:isolation & purification; D005091:Exons; D006801:Humans; D007438:Introns; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics*; D009363:Neoplasm Proteins; D009928:Organ Specificity / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D017433:Protein Structure, Secondary; D051381:Rats; D015842:Serine Proteinase Inhibitors / Q000235:genetics* / Q000378:metabolism; D015843:Serpins / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C484162:PSMD1 protein, human; D010750:Phosphoproteins; C118709:SERPINI2 protein, human; D015842:Serine Proteinase Inhibitors; D015843:Serpins; C083557:p112 protein, rat; D046988:Proteasome Endopeptidase Complex