| The malignant tumor is a complicated disease characterized with inordinate cell cycle, abnormal mitosis and genetic instability. In a certain sense, the malignant tumor is a kind of cell cycle diseases.Human pituitary tumor transforming gene (hPTTG), also termed as Securin, is a key molecular of mitotic spindle checkpoint pathway. hPTTG surveilles orderly progression of cell cycle, ensures the fidelity of cell division and genetic stability, and participates in malignant transformation and tumorigenesis. We cloned and expressed hPTTG, observed its influences on cell cycle, and found that it accelerated cell proliferation and promoted cell malignant transformation. We detected its overexpression in human esophageal tumor tissues compared with the corresponding normal tissues, by using RT-PCR assay and in situ hybridization. On the other hand, the statistical analysis revealed that overexpression of hPTTG was closely associated with tumor differentiation and lymph node metastasis. We further investigated hPTTG's regulation mechanisms, demonstrated that β-catenin/TCF up-regulated hPTTG transcriptional avtivity and its expression. Subsequently, we detected the positive correlation between cytoplasmic accumulation of β-catenin and overexpression of hPTTG in 69 human esophageal tumors. Furthermore, the inhibitors of MAPK pathway could depress hPTTG's transcriptional activity and its expression, indicating that MAPK pathway may regulate hPTTG. We also found that γ-synuclein contributed to the chromosome instability. hPTTG could be up-regulated by γ-synuclein, impling that hPTTG might participate in this chromosome instability progression related with γ-synuclein. hPTTG extensively effected on some important tumor-related genes, it increased expression of oncogene cyclin D1 and anti-apoptosis gene survivin, inhibited Gsk3β kinase activaty, and binded to p53.
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