SV40 T antigen disrupted the cell metabolism and the balance between proliferation and apoptosis in lens tumors of transgenic mice.

Purpose: Simian 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.

Methods: The different lens lesions of alpha A-crystallin/SV40 T antigen transgenic mice were examined using cDNA microarray, immunohistochemistry and TUNEL to scan the influenced molecules and signal pathways.

Results: There 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 1alpha, Mek kinase-1, CK2alpha, 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).

Conclusion: SV40 T antigen remarkably targeted the cell metabolism and disrupted the balance between proliferation and apoptosis during the lens carcinogenesis and following progression.