Annexin II Expression Is Regulated during Mammalian Cell Cycle

Annexin II is a substrate for oncogene and growth factor-associated protein-tyrosine kinases. Elevated expression of annexin II is seen in different types of cancers and recent evidence indicates a role for annexin II in DNA synthesis and cell proliferation. In this report we show that the level of annexin II is subject to cell cycle regulation. Chinese hamster ovary cells were selected without the use of drugs, by the mitotic cell selection technique. As the mitotic cells progressed synchronously through the cell cycle, we determined the steady-state levels of annexin II mRNA and protein. The half-life of annexin II mRNA was approximately 2 h as measured by pulse-chase and ribonuclease protection analyses. Steady-state levels of both annexin II mRNA and protein were high in mitotic cells. As the cells divided and entered G1, there was a reduction in the levels of both annexin II mRNA and protein. New synthesis of annexin II mRNA and protein occurred in early Gi and maximal expression of annexin II mRNA and protein occurred as the cells entered S-phase. A gradual reduction in steady-state levels of annexin II mRNA and protein occurred as cells progressed through S-phase. Similar results were obtained in HeLa cells. In HeLa cells, collected at various cell cycle stages by countercurrent centrifugal elutriation, we observed peak expression of annexin II in G1-S and S-G2 cells. We conclude from our results that annexin II expression is regulated during the mammalian cell cycle.