ANNEXIN-II EXPRESSION IS REGULATED DURING MAMMALIAN-CELL CYCLE

Annexin II is a substrate for oncogene and growth factor-associated pr otein-tyrosine kinases. Elevated expression of annexin II is seen in d ifferent types of cancers and recent evidence indicates a role for ann exin II in DNA synthesis and cell proliferation. In this report we sho w that the level of annexin II is subject to cell cycle regulation. Ch inese hamster ovary cells were selected without the use of drugs, by t he mitotic cell selection technique. As the mitotic cells progressed s ynchronously through the cell cycle, we determined the steady-state le vels of annexin II mRNA and protein. The half-life of annexin II mRNA was approximately 2 h as measured by pulse-chase and ribonuclease prot ection analyses. Steady-state levels of both annexin II mRNA and prote in were high in mitotic cells. As the cells divided and entered G1, th ere was a reduction in the levels of both annexin II mRNA and protein. New synthesis of annexin II mRNA and protein occurred in early G1 and maximal expression of annexin II mRNA and protein occurred as the cel ls entered S-phase. A gradual reduction in steady-state levels of anne xin 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 dur ing the mammalian cell cycle.