Project description:Transcription profiling by array of human gastric cancer cell line AZ-521 with or without doxycycline-induced expresson of dominant-negative Sox2 to study tumorigenic potential of Sox2 in gastric cancer cells
Project description:Gastric cancer is still one of the most common causes of cancer-related death worldwide, which is mainly attributable to late diagnosis and poor treatment options. Infection with H. pylori, different environmental factors and genetic alterations are known to influence the risk of developing gastric tumors. However, the molecular mechanisms involved in gastric carcinogenesis are still not fully understood, making it difficult to design targeted therapeutic approaches. Aberrant expression of the specific gastric differentiation marker Sox2 (sry-related HMG box 2) has been observed in stomach cancer. However, the role of Sox2 in gastric tumors has not been well established to date. To elucidate the role of Sox2 in gastric tumorigenesis, Sox2 transcriptional activity was blocked in AZ521 cells. Interestingly, inhibition of Sox2 reduced cell proliferation and migration, increased apoptosis and induced changes in cell cycle. Blocking of Sox2 also reduced the tumorigenic potential of AZ521 cells in vivo. In addition, correlation of Sox2 expression and proliferation was observed in a subset of human gastric tumours. Finally, target genes of Sox2 were for the first time identified by RNA microarray in gastric cancer cells. Taken together, the results presented here indicate that Sox2 controls several aspects related to gastric cancer development and progression by regulating the expression of members of important signalling pathways. These findings could provide new therapeutic options for a subset of gastric cancers exhibiting Sox2 deregulation. Inducible dnSox2 in AZ521 cells, 4 timepoints with/without induction.
Project description:Gastric cancer is still one of the most common causes of cancer-related death worldwide, which is mainly attributable to late diagnosis and poor treatment options. Infection with H. pylori, different environmental factors and genetic alterations are known to influence the risk of developing gastric tumors. However, the molecular mechanisms involved in gastric carcinogenesis are still not fully understood, making it difficult to design targeted therapeutic approaches. Aberrant expression of the specific gastric differentiation marker Sox2 (sry-related HMG box 2) has been observed in stomach cancer. However, the role of Sox2 in gastric tumors has not been well established to date. To elucidate the role of Sox2 in gastric tumorigenesis, Sox2 transcriptional activity was blocked in AZ521 cells. Interestingly, inhibition of Sox2 reduced cell proliferation and migration, increased apoptosis and induced changes in cell cycle. Blocking of Sox2 also reduced the tumorigenic potential of AZ521 cells in vivo. In addition, correlation of Sox2 expression and proliferation was observed in a subset of human gastric tumours. Finally, target genes of Sox2 were for the first time identified by RNA microarray in gastric cancer cells. Taken together, the results presented here indicate that Sox2 controls several aspects related to gastric cancer development and progression by regulating the expression of members of important signalling pathways. These findings could provide new therapeutic options for a subset of gastric cancers exhibiting Sox2 deregulation.
Project description:Recent studies demonstrated that cancer stem cells (CSCs) have higher tumorigenesis properties than those of differentiated cancer cells and that transcriptional factor-SOX2 plays a vital role in maintaining the unique properties of CSCs; however, the function and underlying mechanism of SOX2 in carcinogenesis of lung cancer are still elusive. This study applied immunohistochemistry to analyze the expression of SOX2 in human lung tissues of normal individuals as well as patients with adenocarcinoma, squamous cell carcinoma, large cell and small cell carcinoma and demonstrated specific overexpression of SOX2 in all types of lung cancer tissues. This finding supports the notion that SOX2 contributes to the tumorigenesis of lung cancer cells and can be used as a diagnostic probe. In addition, obviously higher expression of oncogenes c-MYC, WNT1, WNT2 and NOTCH1 was detected in side population (SP) cells than in none side population (NSP) cells of human lung adenocarcinoma cell line-A549, revealing a possible mechanism for the tenacious tumorigenic potential of CSCs. To further elucidate the function of SOX2 in tumorigenesis of cancer cells, A549 cells were established with expression of luciferase and doxycycline inducible shRNA targeting SOX2. We found silencing of SOX2 gene reduces the tumorigenic property of A549 cells with attenuated expression of c-MYC, WNT1, WNT2 and NOTCH1 in xenografted NOD/SCID mice. By RNA-Seq method, additional 246 target cancer genes of SOX2 were revealed. These results present evidence that SOX2 may regulate the expression of oncogenes in CSCs to promote the development of human lung cancer. Examination of mRNA profiles in A549 cells with SOX2 silencing
Project description:The transcription factor Sox2 inhibits human gastric cancer growth and activates Sox2-related tumor surpressive genes in human gastric cancer cells. Conditional Sox2-overexpression in cells with a low Sox2 level demonstrated that the Sox2-regulated tumor surpressive genes demand on an enhanced Sox2 activity for better expression to work in human gastric cancer. Chromatin immunoprecipitation (ChIP) of Sox2 together with chromatin profiling by ChIP-on-chip analysis demonstrated that Sox2 directly activates the chromatin at promoters or putative enhancers of Sox2 target genes. Transcription factor Sox2 promoter array in MKN28 cells with Sox2 overexpression.
Project description:The transcription factor Sox2 inhibits human gastric cancer growth and activates Sox2-related tumor surpressive genes in human gastric cancer cells. Conditional Sox2-overexpression in cells with a low Sox2 level demonstrated that the Sox2-regulated tumor surpressive genes demand on an enhanced Sox2 activity for better expression to work in human gastric cancer. Chromatin immunoprecipitation (ChIP) of Sox2 together with chromatin profiling by ChIP-on-chip analysis demonstrated that Sox2 directly activates the chromatin at promoters or putative enhancers of Sox2 target genes.
Project description:Recent studies demonstrated that cancer stem cells (CSCs) have higher tumorigenesis properties than those of differentiated cancer cells and that transcriptional factor-SOX2 plays a vital role in maintaining the unique properties of CSCs; however, the function and underlying mechanism of SOX2 in carcinogenesis of lung cancer are still elusive. This study applied immunohistochemistry to analyze the expression of SOX2 in human lung tissues of normal individuals as well as patients with adenocarcinoma, squamous cell carcinoma, large cell and small cell carcinoma and demonstrated specific overexpression of SOX2 in all types of lung cancer tissues. This finding supports the notion that SOX2 contributes to the tumorigenesis of lung cancer cells and can be used as a diagnostic probe. In addition, obviously higher expression of oncogenes c-MYC, WNT1, WNT2 and NOTCH1 was detected in side population (SP) cells than in none side population (NSP) cells of human lung adenocarcinoma cell line-A549, revealing a possible mechanism for the tenacious tumorigenic potential of CSCs. To further elucidate the function of SOX2 in tumorigenesis of cancer cells, A549 cells were established with expression of luciferase and doxycycline inducible shRNA targeting SOX2. We found silencing of SOX2 gene reduces the tumorigenic property of A549 cells with attenuated expression of c-MYC, WNT1, WNT2 and NOTCH1 in xenografted NOD/SCID mice. By RNA-Seq method, additional 246 target cancer genes of SOX2 were revealed. These results present evidence that SOX2 may regulate the expression of oncogenes in CSCs to promote the development of human lung cancer.