The human homolog of the rodent immediate early response genes, PC4 and TIS7, resides in the lung cancer tumor suppressor gene region on chromosome 3p21.
Recently, human chromosome band 3p21.3 was shown to undergo overlapping homozygous deletions in several small cell lung cancer lines further defining a putative tumor suppressor gene(s) region. We report the cloning and mutational analysis of a novel human gene, SKMc15, from the commonly homozygously deleted region in three small cell lung cancer lines (NCI-H1450, NCI-H740, GLC20). It has 11 exons ranging in size from 50 to 541 bp with an open reading frame of 442 amino acids. The gene covers 7 to 10 kb of genomic DNA; the message of 1.8 to 2 kb is expressed in all analyzed fetal and adult human and mouse tissues including heart, brain, placenta, lung liver, skeletal muscle, kidney, testis and pancreas and in small cell and non-small cell cancer lines. The intron/exon boundaries were used to analyze the gene for mutations by exon PCR-SSCP sequencing in 60 small cell lung cancer cell lines. No loss-of-function mutations were detected. The cDNA sequence has high homology, 75% at the protein level, to the rat early response gene PC4 and its murine homolog TIS7. In addition, the known partial sequence of the putative mouse interferon beta2 (64 amino acids) gene is highly conserved in PC4/TIS7 (94%) and in SKMc15 (83%) at the amino acid level. The sequence TAAAT, which is thought to be involved in mRNA degradation, is present in the 3' UTR of SKMc15 and in the 3' UTR of PC4 and TIS7 genes.
Latif
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F
Laboratory of Immunology, SAIC Frederick, NCI-Frederick Cancer Research and Development Center, MD 21702, USA. latif@ncifcrf.gov
Duh
F M
FM
Bader
S
S
Sekido
Y
Y
Li
H
H
Geil
L
L
Zbar
B
B
Minna
J D
JD
Lerman
M I
MI
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D018288:Carcinoma, Small Cell / Q000235:genetics*; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3; D003001:Cloning, Molecular; D004273:DNA, Neoplasm; D016147:Genes, Tumor Suppressor; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics*; D008175:Lung Neoplasms / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D051381:Rats; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; C490045:IFRD1 protein, human; C490043:IFRD2 protein, human; C490044:Ifrd1 protein, mouse; C084979:Ifrd1 protein, rat; C490042:Ifrd2 protein, mouse; D017874:Immediate-Early Proteins; D008565:Membrane Proteins