Induction of tumorigenesis and chromosomal abnormalities in human amniocytes infected with simian virus 40 and kirstein sarcoma virus

Summary Cell cultures of epithelial-like human amniocytes were infected with simian virus 40 (SV40) and Kirsten sarcoma virus (KSV) in various sequential orders, and tested for agar growth, chromosome abnormalities, and tumorigenesis in the nude mouse assay. We observed that regardless of the order in which the viruses were introduced, the doubly infected cells always exhibited the typical SV40 premalignantly transformed phenotype before changing to the malignant phenotype. All doubly transformed cells from different cell donors produced tumors in adult and suckling nude athymic mice, classified as poorly differentiated sarcomas. Infection with SV40 alone conferred extended life span and accelerated growth without, the malignant capability of tumor production. Kirsten sarcoma virus alone produced only focal cell alteration with no change in cell longevity or tumorigenesis. Chromosome studies of the premalignant and malignant cells from one cell donor did not reveal any significant clonal development for marker chromosomes in either cell line. Chromosome 12, which carries the homologous cellular oncogene to KSV, had no increase in aberrations in the malignant cells. Chromosome 8 was most often involved in aberrations, and the most frequent aberration for both series was dicentric chromosomes due to telomere fusion. For other translocations the breakpoints were almost exclusively in the centromere regions. The vulnerability of telomere and centromere regions to the free virus present in these precrisis cells is discussed, and similarities in regard to types of aberrations in transfection experiments are noted.     

An Upstream Open Reading Frame in Phosphatase and Tensin Homolog Encodes a Circuit Breaker of Lactate Metabolism

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Compromising asymmetric stem cell division in Drosophila central brain: Revisiting the connections with tumorigenesis

Asymmetric cell division (ACD) is an essential process during development for generating cell diversity. In addition, a more recent connection between ACD, cancer and stem cell biology has opened novel and highly intriguing venues in the field. This connection between compromised ACD and tumorigenesis was first demonstrated using Drosophila neural stem cells (neuroblasts, NBs) more than a decade ago and, over the past years, it has also been established in vertebrate stem cells. Here, focusing on Drosophila larval brain NBs, and in light of results recently obtained in our lab, we revisit this connection emphasizing two main aspects: 1) the differences in tumor suppressor activity of different ACD regulators and 2) the potential relevance of environment and temporal window frame for compromised ACD-dependent induction of tumor-like overgrowth.     

Rac1促进异质型细胞叠套结构的形成

异质型细胞叠套结构（heterotypic cell-in-cell structure，heCICs）与肿瘤发生和发展密切相关，在生命科学研究中的重要性逐渐显露。Ras相关C3肉毒毒素底物1（Ras-related C3 botulinum toxin substrate 1，Rac1）属于经典的Rho GTP酶，在细胞骨架以及细胞运动中起到关键调控作用。为研究Rac1在heCICs形成中的作用和机制，利用活细胞示踪剂cell-tracker分别标记肿瘤细胞和免疫杀伤细胞，建立heCICs模型。利用Rac1抑制剂NSC23766抑制Rac1活性后发现，肿瘤细胞与免疫杀伤细胞之间的heCICs形成率显著降低。通过分子克隆技术获得重组质粒pQCXIP-Rac1-EGFP，进行病毒包装感染肿瘤细胞获得Rac1过表达细胞系。进一步检测Rac1过表达对heCICs形成能力的影响，结果表明，Rac1表达水平升高后，heCICs形成率显著升高。本研究显示Rac1具有促进heCICs形成的作用，这为Rac1作为细胞叠套相关疾病的药物治疗靶点奠定了研究基础。     

Distinct progenitor behavior underlying neocortical gliogenesis related to tumorigenesis

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The RNA binding protein RALY suppresses p53 activity and promotes lung tumorigenesis

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