Aim:To identify the metastasis suppressor genes for prostate cancer.Methods:A copy of human chromosomeswas introduced into the highly metastatic Dunning R-3327 rat prostate cancer cells by the use of microcell-mediate...Aim:To identify the metastasis suppressor genes for prostate cancer.Methods:A copy of human chromosomeswas introduced into the highly metastatic Dunning R-3327 rat prostate cancer cells by the use of microcell-mediatedchromosome transfer.Relationships between the size of human chromosomes introduced into microcell hybrid clonesand the number of lung metastases produced by the clones were analyzed to determine which part of human chromo-somes contained the metastasis suppressor gene(s)for prostate cancer.To determine portions of human chromosomesintroduced,G-banding chromosomal analysis,fluorescence in sim hybridization analysis,and polymerase chain reac-tion analysis were performed.Results:Each of microcell hybrid clones containing human chromosomes 7,8,10,11,12,or 17 showed decreased ability to metastasize to the lung without any loss of tumorigenicity.This demonstratesthat these human chromosomes contain metastasis suppressor genes for prostate cancer.Spontaneous deletion of portionsof human chromosomes was observed in the human chromosome 7,10,11,12,and 17 studies.In the human chromo-some 8 study,irradiated microcell-mediated chromosome transfer was performed to enrich chromosomal arm deletionsof human chromosome 8.Molecular and cytogenetic analyses of microcell hybrid clones demonstrated that metastasissuppressor genes on human chromosomes were located on 7q21-22,7q31.2-32,8p21-12,10q11-22,11p13-11.2,12p11-q13,12q24-ter,and 17pter-q23.KAII and MKK4/SEKI were identified as metastasis suppressor genes from11p11.2 and 17p12,respectively.Conclusion:This assay system is useful to identify metastasis suppressor gene(s)for prostate cancer.展开更多
Although particular chromosomal syndromes are phenotypicaUy and clinically distinct, the majority of individuals with autosomal imbalance, such as aneuploidy, manifest mental retardation. A common abnormal phenotype o...Although particular chromosomal syndromes are phenotypicaUy and clinically distinct, the majority of individuals with autosomal imbalance, such as aneuploidy, manifest mental retardation. A common abnormal phenotype of Down syndrome （DS）, the most prevalent autosomal aneuploidy, shows a reduction in both the number and the density of neurons in the brain. As a DS model, we have recently created chimeric mice from ES cells containing a single human chromosome 21. The mice mimicked the characteristic phenotypic features of DS, and ES cells showed a higher incidence of apoptosis during early neuronal differentiation in vitro. In this study, we examined the induction of anomalous early neural development by aneuploidy in mouse ES cells by transferring various human chromosomes or additional mouse chromosomes. Results showed an elevated incidence of apoptosis in all autosome-aneuploid clones examined during early neuronal differentiation in vitro. Further, cDNA microarray analysis revealed a common cluster of down-regulated genes, of which eight known genes are related to cell proliferation, neurite outgrowth and differentiation. Importantly, targeting of these genes by siRNA knockdown in normal mouse ES cells led to enhanced apoptosis during early neuronal differentiation. These findings strongly suggest that autosomal imbalance is associated with general neuronal loss through a common molecular mechanism for apoptosis.展开更多
基金These studies were supported in part by Grant-in-Aid for Scientific Research(A)from Japan Sociely for the Promotion of Science(11307029)Grant-in-Aid of The Japan Medical Association(1999).
文摘Aim:To identify the metastasis suppressor genes for prostate cancer.Methods:A copy of human chromosomeswas introduced into the highly metastatic Dunning R-3327 rat prostate cancer cells by the use of microcell-mediatedchromosome transfer.Relationships between the size of human chromosomes introduced into microcell hybrid clonesand the number of lung metastases produced by the clones were analyzed to determine which part of human chromo-somes contained the metastasis suppressor gene(s)for prostate cancer.To determine portions of human chromosomesintroduced,G-banding chromosomal analysis,fluorescence in sim hybridization analysis,and polymerase chain reac-tion analysis were performed.Results:Each of microcell hybrid clones containing human chromosomes 7,8,10,11,12,or 17 showed decreased ability to metastasize to the lung without any loss of tumorigenicity.This demonstratesthat these human chromosomes contain metastasis suppressor genes for prostate cancer.Spontaneous deletion of portionsof human chromosomes was observed in the human chromosome 7,10,11,12,and 17 studies.In the human chromo-some 8 study,irradiated microcell-mediated chromosome transfer was performed to enrich chromosomal arm deletionsof human chromosome 8.Molecular and cytogenetic analyses of microcell hybrid clones demonstrated that metastasissuppressor genes on human chromosomes were located on 7q21-22,7q31.2-32,8p21-12,10q11-22,11p13-11.2,12p11-q13,12q24-ter,and 17pter-q23.KAII and MKK4/SEKI were identified as metastasis suppressor genes from11p11.2 and 17p12,respectively.Conclusion:This assay system is useful to identify metastasis suppressor gene(s)for prostate cancer.
文摘Although particular chromosomal syndromes are phenotypicaUy and clinically distinct, the majority of individuals with autosomal imbalance, such as aneuploidy, manifest mental retardation. A common abnormal phenotype of Down syndrome （DS）, the most prevalent autosomal aneuploidy, shows a reduction in both the number and the density of neurons in the brain. As a DS model, we have recently created chimeric mice from ES cells containing a single human chromosome 21. The mice mimicked the characteristic phenotypic features of DS, and ES cells showed a higher incidence of apoptosis during early neuronal differentiation in vitro. In this study, we examined the induction of anomalous early neural development by aneuploidy in mouse ES cells by transferring various human chromosomes or additional mouse chromosomes. Results showed an elevated incidence of apoptosis in all autosome-aneuploid clones examined during early neuronal differentiation in vitro. Further, cDNA microarray analysis revealed a common cluster of down-regulated genes, of which eight known genes are related to cell proliferation, neurite outgrowth and differentiation. Importantly, targeting of these genes by siRNA knockdown in normal mouse ES cells led to enhanced apoptosis during early neuronal differentiation. These findings strongly suggest that autosomal imbalance is associated with general neuronal loss through a common molecular mechanism for apoptosis.
