Infrequent mutations of the activating transcription factor-2 gene in human lung cancer, neuroblastoma and breast cancer.
The activating transcription factor 2 (ATF-2) gene, which encodes a transcription factor involved in multiple intracellular signal transduction pathways, is located on human chromosome 2q32, which is a common region of LOH in human lung cancer. In neuroblastoma and breast cancer, a high incidence of LOH was detected on chromosome 2q. Recently we found that breast cancer is frequently developed in heterozygous mutant mice for the ATF-2 gene. Therefore, the ATF-2 gene was considered as a candidate tumor suppressor gene on 2q. To assess the role of the ATF-2 gene as a tumor suppressor in human carcinogenesis, we examined genetic alterations of the ATF-2 gene in 9 breast cancer cell lines, 10 neuroblastoma cell lines and 46 lung cancer cell lines. For this purpose, we first determined the exon-intron structure of the ATF-2 gene in the human genome. The ATF-2 gene was composed of 14 exons and 13 introns, and the ATG start codon and the TGA stop codon were present in exons 3 and 14, respectively. Genetic variants of the ATF-2 gene were detected in 5 of the 46 (10.6%) lung cancers, but not in neuroblastomas and breast cancers. Three of the five variants detected in lung cancers were genetic polymorphisms, while the remaining two, consisting of non-synonymous and synonymous substitutions, were possibly somatic mutations. The present result indicates that the ATF-2 gene is not a major tumor suppressor gene on chromosome 2q, however, it is possible that ATF-2 alterations may be involved in the development of a small subset of lung cancers.
Woo
In Sook
IS
Biology Division, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
Kohno
Takashi
T
Inoue
Kaoru
K
Ishii
Shunsuke
S
Yokota
Jun
J
D051698:Activating Transcription Factor 2; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics*; D002889:Chromosomes, Human, Pair 2; D003062:Codon; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics*; D004247:DNA / Q000378:metabolism; D005091:Exons; D014644:Genetic Variation; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007438:Introns; D008175:Lung Neoplasms / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D009447:Neuroblastoma / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011487:Protein Conformation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics*
C497105:ATF2 protein, human; D051698:Activating Transcription Factor 2; D003062:Codon; D017362:Cyclic AMP Response Element-Binding Protein; D014157:Transcription Factors; D004247:DNA