SV40 T antigen disrupted the cell metabolism and the balance between proliferation and apoptosis in lens tumors of transgenic mice
SV40 T antigen disrupted the cell metabolism and the balance between proliferation and apoptosis in lens tumors of transgenic mice
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DOI：
10.1007/s00432-009-0599-z
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发表时间：
2009-05
影响因子：
3.6
通讯作者：
Hua-Chuan Zheng;Takafumi Nakamura;Yang-Yu Zheng;Yuko Nakanishi;Y. Tabuchi;A. Uchiyama;Hiroyuki Takahashi;Y. Takano
中科院分区：
文献类型：
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作者：
Hua-Chuan Zheng;Takafumi Nakamura;Yang-Yu Zheng;Yuko Nakanishi;Y. Tabuchi;A. Uchiyama;Hiroyuki Takahashi;Y. Takano
目的猴Vacuolating病毒40(SV40)T抗原干扰P53和Rb，引起细胞恶性转化。方法应用基因芯片、免疫组织化学和原位末端标记法对αA-晶体蛋白/SV40T抗原转基因小鼠晶状体的不同病变进行分子和信号通路扫描。结果在晶状体病变过程中出现异型增生、原位癌、继发眼内外侵袭、淋巴结和肺转移。自从晶状体癌发生以来，细胞功能从细胞周期、细胞形态、细胞发育、细胞间信号转导等多个方面发生了很大的变化。在碳水化合物、氨基酸、核苷酸、外源物质和氮代谢等信号通路上有显著差异(P<；P<；005)，在肿瘤开始侵袭后，细胞增殖和细胞死亡也有显著差异。自从发生眼球外癌侵袭以来，细胞生长、细胞周期、细胞间信号和代谢发生了显著的变化。在野生型小鼠晶状体中未见纤维蛋白原、Stat1α、MEKK1、CK2α、GRP78、Arp2和Apr3的表达。异型增生、原位癌和眼球内浸润性癌的增殖水平显著高于其他组(P<；P<0.05)。异型增生组织的细胞凋亡率明显高于野生型对照组(P<；<0.05)，但低于其他组(P<；<0.05)。结论SV40T抗原显著靶向细胞代谢，破坏晶状体癌发生和发展过程中增殖与凋亡的平衡。
PurposeSimian Vacuolating Virus 40 (SV40) T antigen perturbed p53 and RB to cause cell malignant transformation. The purpose of this study was to identify the molecular changes during lens carcinogenesis and cancer progression induced by SV40 T antigen.MethodsThe different lens lesions of α A-crystallin/SV40 T antigen transgenic mice were examined using cDNA microarray, immunohistochemistry and TUNEL to scan the influenced molecules and signal pathways.ResultsThere appeared dysplasia, carcinoma in situ, followed by invasion inside or outside eyeball, and final metastasis into lymph node or lung. Cell functions largely changed from such many aspects as cell cycle, cell morphology, cell development, cell-to-cell signaling and so forth since lens carcinogenesis. The significant differences were observed in such signaling pathways as metabolism about carbohydrate, amino acid, nucleotides, Xenobiotics and nitrogen (P< 0.05).The remarkable distinction of cell proliferation and cell death was found after carcinoma began to invade. There was significant alteration in cell growth, cell cycle, cell-to-cell signaling and metabolism since carcinoma invasion outside the eyeball happened. Parafibromin, Stat 1α, Mek kinase-1, CK2α, GRP78, Arp2 and Apr3 were not expressed in wild-type mice lens, but in others. The proliferative levels of dysplasia, carcinoma in situ and invasive carcinoma inside eyeballs were statistically higher than other groups (P< 0.05). The apoptotic levels of dysplasia were significantly higher than wild-type control (P< 0.05), but lower than the others (P< 0.05).ConclusionSV40 T antigen remarkably targeted the cell metabolism and disrupted the balance between proliferation and apoptosis during the lens carcinogenesis and following progression.