The regulation of polyamine biosynthesis during the cell cycle in synchronously growing cells
Much effort today is put into studying the regulation of polyamine biosynthesis at the molecular level. We intend to utilize that knowledge to clarify the regulation of polyamine biosynthesis throughout the phases of the cell cycle and put this into the context of other cell cycle regulatory pathways including those involved in signal transduction. If we wish to treat cancer through manipulating the polyamine pools, we first have to elucidate the factors involved in polyamine homeostasis in normal cells.
Cultures of MCF-10A normal breast epithelial cells are used because of their short cell cycle time. Also, this kind of study has never been performed with normal human cells. With the mitotic shake off technique, we obtain cell populations that progress unperturbedly and synchronously through the cell cycle.
Control of polyamine biosynthesis during the cell cycle
We are investigating all aspects of polyamine homeostasis from the mRNA to the protein and enzyme activity levels. Enzymes we are investigating are: ornithine decarboxylase, S-adenosylmethionine decarboxylase, spermine synthase, spermidine synthase, spermine oxidase, spermidine/spermine-N1 acetylase, polyamine oxidase, antizyme and antizyme inhibitor.