Counteraction of pRb-dependent protection after extreme hypoxia by elevated ribonucleotide reductase

Cell Proliferation
Pål GraffE O Pettersen

Abstract

We have studied hypoxia-induced cell cycle arrest in human cells where the retinoblastoma tumour suppressor protein (pRb) is either functional (T-47D and T-47DHU-res cells) or abrogated by expression of the HPV18 E7 oncoprotein (NHIK 3025 cells). We have previously found that pRb is dephosphorylated and rebound in the nucleus in T-47D cells arrested in S-phase during hypoxia and that this binding is protracted even following re-oxygenation. In the present study, however, we show that the long-lasting arrest following re-oxygenation induced by pRb-binding in the cell nuclei may be overruled by an elevated level of ribonucleotide reductase (RNR). This seems to create a forced DNA-synthesis, uncoordinated with cell division, which induces endoreduplication of the DNA. The data indicate that the cells initiating endoreduplication continue DNA-synthesis until all DNA is replicated once and then may start cycling and cell division with a doubled DNA-content. Corresponding data on the pRb-incompetent NHIK 3025-cells show similar endoreduplication in these. Thus, the data indicate that endoreduplication of DNA following re-oxygenation may come, either as a result of hypoxic arrest of DNA-synthesis when pRb-function is absent in the cel...Continue Reading

References

May 1, 1979·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·I KeydarH J Brenner
Aug 30, 1989·Biochemical and Biophysical Research Communications·H ProbstK Scheffler
Dec 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·S D YoungR P Hill
Feb 10, 1983·Biochemical and Biophysical Research Communications·L ThelanderM Thelander
Mar 1, 1981·British Journal of Cancer·E O Pettersen, T Lindmo
Jan 1, 1993·Experimental Cell Research·T StokkeH B Steen
Dec 2, 1999·Experimental Cell Research·R Baserga
Jun 24, 2000·International Journal of Radiation Biology·E K Rofstad
Sep 26, 2000·Molecular and Cellular Biology·K E KnudsenE S Knudsen
Feb 14, 2002·Progress in Biophysics and Molecular Biology·H EklundP Nordlund
Jan 10, 2003·Seminars in Radiation Oncology·Bradly G WoutersPhilippe Lambin
Mar 12, 1962·Biochimica Et Biophysica Acta·G FROESE

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Nov 14, 2008·Journal of Enzyme Inhibition and Medicinal Chemistry·Dharmarajan SriramPerumal Yogeeswari
Jul 25, 2012·ACS Chemical Biology·Florian SchmitzbergerPär Nordlund
Dec 17, 2014·International Journal of Radiation Biology·Nina Jeppesen EdinErik Olai Pettersen
Aug 24, 2004·The Journal of Biological Chemistry·Kari R StrandK Kristoffer Andersson
May 28, 2005·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Jørund SollidGöran E Nilsson
Apr 3, 2009·Journal of Enzyme Inhibition and Medicinal Chemistry·Peter EbbesenAndrea Scozzafava

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