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Angiogenin Is Translocated to the Nucleus of HeLa Cells and Is Involved in Ribosomal RNA Transcription and Cell Proliferation

Center for Biochemical and Biophysical Sciences and Medicine, Department of Pathology, Harvard Medical School, Boston, Massachusetts

Requests for reprints: Guo-fu Hu, Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, MA 02115. Phone: 617-432-6582; Fax: 617-432-6580; E-mail: guofu_hu{at}hms.harvard.edu.

Angiogenin is an angiogenic protein known to play a role in rRNA transcription in endothelial cells. Nuclear translocation of angiogenin in endothelial cells decreases as cell density increases and ceases when cells are confluent. Here we report that angiogenin is constantly translocated to the nucleus of HeLa cells in a cell density–independent manner. Down-regulation of angiogenin expression by antisense and RNA interference results in a decrease in rRNA transcription, ribosome biogenesis, proliferation, and tumorigenesis both in vitro and in vivo. Exogenous angiogenin rescues the cells from antisense and RNA interference inhibition. The results showed that angiogenin is constitutively translocated into the nucleus of HeLa cells where it stimulates rRNA transcription. Thus, besides its angiogenic activity, angiogenin also plays a role in cancer cell proliferation.

Key Words: rRNA transcription • cell proliferation • cancer progression • angiogenin • nuclear translocation

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