Author/Authors :
Gen، نويسنده , , Yasuyuki and Yasui، نويسنده , , Kohichiroh and Zen، نويسنده , , Yoh and Zen، نويسنده , , Keika and Dohi، نويسنده , , Osamu and Endo، نويسنده , , Mio and Tsuji، نويسنده , , Kazuhiro and Wakabayashi، نويسنده , , Naoki and Itoh، نويسنده , , Yoshito and Naito، نويسنده , , Yuji and Taniwaki، نويسنده , , Masafumi and Nakanuma، نويسنده , , Yasuni and Okanoue، نويسنده , , Takeshi and Yoshikawa، نويسنده , , Tosh، نويسنده ,
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.
