title: SOX2 identified as a target gene for the amplification at 3q26 that is frequently detected in esophageal squamous cell carcinoma.
abstract: SOX2 is a transcription factor with a high-mobility group DNA-binding domain that functions as a master regulator during embryogenesis and organogenesis. We investigated DNA copy number aberrations in esophageal squamous cell carcinoma (ESCC) cell lines using a high-density oligonucleotide microarray and found frequent amplification at the chromosomal region 3q26. The estimated extent of the minimal overlapping region of amplification was 1.3 Mb. This chromosomal region includes a single gene, SOX2. The SOX2 protein was overexpressed in cell lines in which the gene was amplified. Knockdown experiments showed that SOX2 promotes proliferation of ESCC cells. Genes potentially modulated by SOX2 were determined by expression array analyses combined with small interfering RNA cell-transfection studies. A copy number gain of SOX2 (>2-fold) was observed in 6 of the 40 primary ESCCs (15%). Immunohistochemical study revealed that expression of the SOX2 protein was significantly elevated in 62 of the 89 ESCC tumors (70%), compared with their nontumorous counterparts, and that upregulated expression of SOX2 was associated with poor differentiation of ESCC. Our results suggest that SOX2 is likely to be a target of the 3q26 amplification and may therefore be involved in the development or progression of ESCC.
authors.affiliation: Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Gen
authors.forename: Kohichiroh
authors.initials: K
authors.lastname: Yasui
authors.forename: Yoh
authors.initials: Y
authors.lastname: Zen
authors.forename: Keika
authors.initials: K
authors.lastname: Zen
authors.forename: Osamu
authors.initials: O
authors.lastname: Dohi
authors.forename: Mio
authors.initials: M
authors.lastname: Endo
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tsuji
authors.forename: Naoki
authors.initials: N
authors.lastname: Wakabayashi
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Itoh
authors.forename: Yuji
authors.initials: Y
authors.lastname: Naito
authors.forename: Masafumi
authors.initials: M
authors.lastname: Taniwaki
authors.forename: Yasuni
authors.initials: Y
authors.lastname: Nakanuma
authors.forename: Takeshi
authors.initials: T
authors.lastname: Okanoue
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Yoshikawa
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D056915:DNA Copy Number Variations / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D005784:Gene Amplification; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D034741:RNA, Small Interfering / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D034741:RNA, Small Interfering; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins