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  • Original Paper
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pRB and p107 have distinct effects when expressed in pRB-deficient tumor cells at physiologically relevant levels

Abstract

A key difference among the three structurally similar pRB family members is that only pRB is a tumor suppressor. Identification of distinctive functional differences between pRB and p107/p130 therefore holds promise for a better understanding of the tumor suppression mechanisms of pRB. Enigmatically, pRB and p107 have been shown to have indistinguishable growth suppression activities when studied in the pRB-deficient Saos-2 cell system. In this study, we discovered that, when expressed at physiologically relevant levels, pRB and p107 had distinctive effects in causing growth suppression. pRB induced cellular p130 levels while p107 repressed them. p107, but not pRB, blocked cells inside S phase in addition to G1 arrest. In contrast, no qualitative differences were identified in their abilities to repress the expression of a set of suspected pRB/E2F repression target genes. These results indicate that pRB and p107 possess different growth suppression effects, despite the fact that they have similar E2F repression effects.

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Acknowledgements

We thank all colleagues who contributed to our studies by providing us with invaluable reagents (acknowledged in Materials and methods), and D Gebhard for assistance with FACS analysis. We thank Oyinkansola Ogunrinde for constructing the pUHD10-3p130 plasmid. L Zhu is indebted to Ed Harlow, in whose laboratory the first pRB inducible cell line was established. This work was supported by the American Cancer Society Research Project Grant (97-125-01). Albert Einstein Comprehensive Cancer Research Center Grant provided support for core services. AN Karnezis is supported by the Medical Scientist Training Program at the Albert Einstein College of Medicine and L Zhu is a Leukemia & Lymphoma Society Scholar.

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Jiang, H., Karnezis, A., Tao, M. et al. pRB and p107 have distinct effects when expressed in pRB-deficient tumor cells at physiologically relevant levels. Oncogene 19, 3878–3887 (2000). https://doi.org/10.1038/sj.onc.1203722

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