SOX2 identified as a target gene for the amplification at 3q26 that is frequently detected in esophageal squamous cell carcinoma.
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.
Gen
Yasuyuki
Y
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto, Japan.
Yasui
Kohichiroh
K
Zen
Yoh
Y
Zen
Keika
K
Dohi
Osamu
O
Endo
Mio
M
Tsuji
Kazuhiro
K
Wakabayashi
Naoki
N
Itoh
Yoshito
Y
Naito
Yuji
Y
Taniwaki
Masafumi
M
Nakanuma
Yasuni
Y
Okanoue
Takeshi
T
Yoshikawa
Toshikazu
T
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
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