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Aurora-A/BTAK/STK15 gene which encodes a centrosome-associated kinase is located on chromosome 20q13.2, a highly amplified region in various human tumors. Recent studies have demonstrated the overexpression and amplification of Aurora-A in many malignant human cancers. The purpose of this study was to investigate the amplification and expression of Aurora-A in esophageal squamous cell carcinoma. Amplification of Aurora-A was determined by fluorescence in situ hybridization in 7 esophageal cancer cell lines and real-time PCR in 29 esophageal cancer samples. We detected Aurora-A expression in 7 esophageal cancer cell lines and 38 esophageal cancers samples by semi-quantitative reverse transcription-PCR and Western blot hybridization. The amplification of Aurora-A was detected in 27 of 29 (93.1%) esophageal cancer samples and 6 of 7 (85.7%) cancer cell lines. Aurora-A was overexpressed in 27 of 38 (71.1%) esophageal cancer samples and all 7 esophageal cancer cell lines. We conclude that Aurora-A is amplified and overexpressed in esophageal squamous cancer.

To detect the expression of survivin in esophageal cancer and elucidate its function in esophageal cancer.Expression of surviv in was detected in paired normal and tumor tissues from patients with esophageal cancer by semi-quantitative RT-PCR. A dominant-negative survivin (surT34A) was transfected into esophageal cancer EC9706 cells (EC9706surT34A). Colony formation and apoptosis of the parental and surT34A-transfected EC9706 cells were examined in soft agar and by flow cytometry, respectively.Survivin mRNA expression of tumor tissues was higher than normal tissues in 18/27 (66.7%) samples. The expression level of survivin mRNA in tumor tissues (2.08 +/- 1.32) was significantly higher than that in normal tissues (1.22 +/- 1.09). EC9706 surT34A cells formed fewer colonies on agar than the non-transfected ones. After serum withdrawal, EC9706surT34A had higher apoptotic ratio than control, but survivin could reduce the apoptotic ratio.Overexpression of survivin is a common eventin esophageal cancer. The dominant-negative survivin can partially inhibit the malignant phenotype of esophageal cancer.

Although Wnt pathway plays important role in colorectal carcinogenesis, but the mechanism of this pathway in anti-apoptosis is not clear. This study is to investigate the molecular mechanism of Wnt pathway in anti-apoptosis.Survivin promoter region was constructed into luciferase reporter system (pGL3-sur1.8kb). The recombinants pGL3-sur1.8kb were cotransfected with pRL-SV40 into HCT116 cells and the activities were detected with Dual-luciferase reporter assay system. Cell apoptosis was analyzed by flow cytometry. Protein level of survivin and beta-catenin was detected by Western Blot.Survivin could be up-regulated by beta-catenin and down-regulated by TCF4DeltaN in transcriptional level. beta-catenin/TCF4 dependent apoptosis induced by indomethacin could suppress survivin transcription. Overexpression of survivin could partially recover the beta-catenin/TCF4 dependent apoptosis.Down-regulation of survivin affected by beta-catenin/TCF4 pathway plays an important role in apoptosis induced by NSAIDs indomethacin in HCT116 cells. The beta-catenin/TCF4-survivin pathway may be a potential target in treatment of colon cancer.

Introduction Breast cancer is the leading cause of cancer death in women worldwide. Elevated expression of c-Myc is a frequent genetic abnormality seen in this malignancy. For a better understanding of its role in maintaining the malignant phenotype, we used RNA interference (RNAi) directed against c-Myc in our study. RNAi provides a new, reliable method to investigate gene function and has the potential for gene therapy. The aim of the study was to examine the anti-tumor effects elicited by a decrease in the protein level of c-Myc by RNAi and its possible mechanism of effects in MCF-7 cells. Method A plasmid-based polymerase III promoter system was used to deliver and express short interfering RNA (siRNA) targeting c-myc to reduce its expression in MCF-7 cells. Western blot analysis was used to measure the protein level of c-Myc. We assessed the effects of c-Myc silencing on tumor growth by a growth curve, by soft agar assay and by nude mice experiments in vivo. Standard fluorescence-activated cell sorter analysis and TdT-mediated dUTP nick end labelling assay were used to determine apoptosis of the cells. Results Our data showed that plasmids expressing siRNA against c-myc markedly and durably reduced its expression in MCF-7 cells by up to 80%, decreased the growth rate of MCF-7 cells, inhibited colony formation in soft agar and significantly reduced tumor growth in nude mice. We also found that depletion of c-Myc in this manner promoted apoptosis of MCF-7 cells upon serum withdrawal. Conclusion c-Myc has a pivotal function in the development of breast cancer. Our data show that decreasing the c-Myc protein level in MCF-7 cells by RNAi could significantly inhibit tumor growth both in vitro and in vivo, and imply the therapeutic potential of RNAi on the treatment of breast cancer by targeting overexpression oncogenes such as c-myc, and c-myc might be a potential therapeutic target for human breast cancer.

Survivin was aberrantly expressed in most cancer tissues, suggesting that survivin plays an important role in carcinogenesis. This study was designed to investigate the function and mechanism of survivin mutants in tumor cells.The site-mutant and truncated survivin mutants were transfected into HeLa cells and selected using G418. Cell apoptosis was analyzed using flow cytometry. Protein level of cyclin D1 was detected by Western blot analysis.Survivin mutant plasmid expressed in the HeLa cells successfully. The expressed protein could be detected using related antibody. Colony formation ability significantly decreased in the HeLa cells with survivin mutants compared with that in the parental HeLa cells. The HeLa cells transfected instantly with survivin mutants could undergo apoptosis automatically. Meanwhile, survivin mutants could cause an increase of multinuclear HeLa cells. The effect of survivin-N showed more effective than that of survivin T34A. Survivin-N and survivin T34A could influence the expression of cyclin D1 and reduced its protein levels of 68% and 12%, respectively.Survivin mutants can partially reverse the malignancy of HeLa cells. The reduction of cyclin D1 induced by survivin mutants may play an important role in it. Survivin may be a target gene in gene therapy of cancer.