Primary research

Polyamine depletion induces G₁ and S phase arrest in human retinoblastoma Y79 cells

Akiko Ueda¹ , Makoto Araie¹ and Shunichiro Kubota²

¹Department of Ophthalmology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan

²Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo 153-8902, Japan

author email corresponding author email

Cancer Cell International 2008, 8:2doi:10.1186/1475-2867-8-2

Published:	21 January 2008

Abstract

Background

Polyamines and ornithine decarboxylase (ODC) are essential for cell proliferation. DL-α-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.

Conclusion

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.