Polyamine depletion induces G1 and S phase arrest in human retinoblastoma Y79 cells.
BACKGROUND
Polyamines and ornithine decarboxylase (ODC) are essential for cell proliferation. DL-alpha-difluoromethylornithine (DFMO), a synthetic inhibitor of ODC, induces G1 arrest through dephosphorylation of retinoblastoma protein (pRb). The effect of DFMO on cell growth of pRb deficient cells is not known. We examined the effects of DFMO on pRb deficient human retinoblastoma Y79 cell proliferation and its molecular mechanism.


METHODS
Using cultured Y79 cells, the effects of DFMO were studied by using polyamine analysis, western blot, gel shift, FACS and promoter analysis.


RESULTS
DFMO suppressed the proliferation of Y79 cells, which accumulated in the G1 and S phase. DFMO induced p27/Kip1 protein expression, p107 dephosphorylation and accumulation of p107/E2F-4 complex in Y79 cells.


CONCLUSIONS
These results indicate that p107 dephosphorylation and accumulation of p107/E2F-4 complex is involved in G1 and S phase arrest of DFMO treated Y79 cells.
Ueda
Akiko
A
Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo 153-8902, Japan. aueda-tky@umin.ac.jp
Araie
Makoto
M
Kubota
Shunichiro
S