| Angiogenin was isolated as a tumor angiogenic factor based solely on its angiogenicactivity. Angiogenin undergoes nuclear translocation in endothelial cells where itaccumulates in the nucleolus and stimulates rRNA transcription, which is essential forangiogenesis. Many studies have mainly focused on how it induces angiogenesis, whichallows further tumor growth and metastasis. Here, we investigated the effects of angiogeninon melanoma cells growth and studied its influence on the expression and function of basicfibroblast growth factor (bFGF). We transfected angiogenin gene in the sense and antisenseorientation into A375 cells, and obtained stable angiogenin under-expressing andover-expressing transfectants. We found that in the angiogenin antisense transfectants, the cellproliferation was decreased and the bFGF induced cell proliferation was inhibited, but theexpression of bFGF was increased. In contrast, in the angiogenin sense transfectants, the cellproliferation was increased, and the bFGF induced cell proliferation was also increased.However, the expression of bFGF was decreased. We also demonstrated that angiogeninundergoes nuclear translocation in A375 cells. The electron microscopy assay shows thatangiogenin was located in DFCs, where rDNA was mainly situated and the synthesis of rRNAtook place. Neomycin inhibits nuclear translocation of angiogenin and abolishesangiogenin-induced A375 cell proliferation. In conclusion, we demonstrated that besides itsangiogenic activity, angiogenin also directly contributes to A375 cell proliferation byundergoing nuclear translocation. Neomycin inhibits the nuclear translocation of angiogenin,therefore inhibits angiogenin-induced cell proliferation. We also demonstrated that angiogeninis required for the bFGF to induce cell proliferation. The endogenous angiogenin expressionlevels affect the expression of bFGF in A375 cells. Targeting angiogenin, therefore, may finda potential therapeutic approach in human malignant melanoma.
|
PDF Full Text Request