The miniature chromosome maintenance(MCM)complex is a group of proteins that are essential for DNA replication licensing and control of cell cycle progression from G1 to S phase.Recent studies suggest that MCM7 is ove...The miniature chromosome maintenance(MCM)complex is a group of proteins that are essential for DNA replication licensing and control of cell cycle progression from G1 to S phase.Recent studies suggest that MCM7 is overexpressed and amplified in a variety of human malignancies.MCM7 genome sequence contains a cluster of miRNA that has been shown to downregulate expression of several tumor suppressors including p21,E2F1,BIM and pTEN.The oncogenic potential of MCM7 and its embedded miRNA has been demonstrated vigorously in in vitro experiments and in animal models,and they appear to cooperate in initiation of cancer.MCM7 protein also serves as a critical target for oncogenic signaling pathways such as androgen receptor signaling,or tumor suppressor pathways such as integrinα7 or retinoblastoma signaling.This review analyzes the transforming activity and signaling of MCM7,oncogenic function of miRNA cluster that is embedded in the MCM7 genome,and the potential of gene therapy that targets MCM7.展开更多
Elizabeth Fisher and Victor collaboratively for many years on Tybulewicz have worked the Down syndrome mouse model project. Elizabeth Fisher＇s background is in molecular genetics and mouse models, with an interest in...Elizabeth Fisher and Victor collaboratively for many years on Tybulewicz have worked the Down syndrome mouse model project. Elizabeth Fisher＇s background is in molecular genetics and mouse models, with an interest in anueploidy. Victor Tybulewicz is an immunologist whose primary interest is in signal transduction from the antigen receptors of B and T cells.展开更多
AIM： To determine allelic imbalance on chromosomal region 21q22-qter including trefoil factor family genes （TFF） in cholangiocarcinoma （CCA） patients and analyze the correlation between allelic imbalances and cli...AIM： To determine allelic imbalance on chromosomal region 21q22-qter including trefoil factor family genes （TFF） in cholangiocarcinoma （CCA） patients and analyze the correlation between allelic imbalances and clinicopathological parameters. METHODS： Quantitative PCR amplification was performed on four microsatellite markers and trefoil factor family genes （TFF1, TFF2, and TFF3） using a standard curve and SYBR Green I dye method. The relative copy number was determined by DNA copy number of tested locus to reference locus. The relative copy number was interpreted as deletion or amplification by comparison with normal reference range. Associations between allelic imbalance and clinicopathological parameters of CCA patients were evaluated by χ^2-tests. Kaplan-Meier method was used to analyze survival. RESULTS： The frequencies of amplification at D21S1890, D21S1893, and TFF3 were 32.5%, 30.0%, and 28.7%, respectively. Patients who had amplification at regions covering D21S1893, D21S1890, and TFF showed poor prognosis, whereas patients who had deletion showed favorable prognosis （mean： 51.7 wk vs 124.82 wk, P = 0.012）. Multivariate Cox regression analysis revealed that amplification of D21S1893, D21S1890 and TFF, blood vessel invasion, and staging were associated with poor prognosis. CONCLUSION： D21S1893-D21S1890 region may harbor candidate genes especially TFF and serine protease family, which might be involved in tumor invasion and metastasis contributing to poor survival. The amplification in this region may be used as a prognostic marker in the treatment of CCA patients.展开更多
文摘The miniature chromosome maintenance(MCM)complex is a group of proteins that are essential for DNA replication licensing and control of cell cycle progression from G1 to S phase.Recent studies suggest that MCM7 is overexpressed and amplified in a variety of human malignancies.MCM7 genome sequence contains a cluster of miRNA that has been shown to downregulate expression of several tumor suppressors including p21,E2F1,BIM and pTEN.The oncogenic potential of MCM7 and its embedded miRNA has been demonstrated vigorously in in vitro experiments and in animal models,and they appear to cooperate in initiation of cancer.MCM7 protein also serves as a critical target for oncogenic signaling pathways such as androgen receptor signaling,or tumor suppressor pathways such as integrinα7 or retinoblastoma signaling.This review analyzes the transforming activity and signaling of MCM7,oncogenic function of miRNA cluster that is embedded in the MCM7 genome,and the potential of gene therapy that targets MCM7.
基金the Brain Research Trust,the Wellcome Trust,the UK Medical Research Council and the AnEUploidy grant from Framework Programme 6 from the European Union Commission for funding
文摘Elizabeth Fisher and Victor collaboratively for many years on Tybulewicz have worked the Down syndrome mouse model project. Elizabeth Fisher＇s background is in molecular genetics and mouse models, with an interest in anueploidy. Victor Tybulewicz is an immunologist whose primary interest is in signal transduction from the antigen receptors of B and T cells.
基金Supported by the Research Grants from Khon Kaen University, No. 48-03-1-01-03 the Center for Research and Development in Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, No 06-01
文摘AIM： To determine allelic imbalance on chromosomal region 21q22-qter including trefoil factor family genes （TFF） in cholangiocarcinoma （CCA） patients and analyze the correlation between allelic imbalances and clinicopathological parameters. METHODS： Quantitative PCR amplification was performed on four microsatellite markers and trefoil factor family genes （TFF1, TFF2, and TFF3） using a standard curve and SYBR Green I dye method. The relative copy number was determined by DNA copy number of tested locus to reference locus. The relative copy number was interpreted as deletion or amplification by comparison with normal reference range. Associations between allelic imbalance and clinicopathological parameters of CCA patients were evaluated by χ^2-tests. Kaplan-Meier method was used to analyze survival. RESULTS： The frequencies of amplification at D21S1890, D21S1893, and TFF3 were 32.5%, 30.0%, and 28.7%, respectively. Patients who had amplification at regions covering D21S1893, D21S1890, and TFF showed poor prognosis, whereas patients who had deletion showed favorable prognosis （mean： 51.7 wk vs 124.82 wk, P = 0.012）. Multivariate Cox regression analysis revealed that amplification of D21S1893, D21S1890 and TFF, blood vessel invasion, and staging were associated with poor prognosis. CONCLUSION： D21S1893-D21S1890 region may harbor candidate genes especially TFF and serine protease family, which might be involved in tumor invasion and metastasis contributing to poor survival. The amplification in this region may be used as a prognostic marker in the treatment of CCA patients.
