A mathematical model of the regulation of the G1 phase of Rb+/+ and Rb-/- mouse embryonic fibroblasts and an osteosarcoma cell line

M. N. Obeyesekere; E. S. Knudsen; J. Y J Wang; S. O. Zimmerman

doi:10.1111/j.1365-2184.1997.tb00933.x

A mathematical model of the regulation of the G₁ phase of Rb+/+ and Rb-/- mouse embryonic fibroblasts and an osteosarcoma cell line

M. N. Obeyesekere, E. S. Knudsen, J. Y J Wang, S. O. Zimmerman

Pathology

Research output: Contribution to journal › Article › peer-review

27 Scopus citations

Abstract

A mathematical model integrating the roles of cyclin D, cdk4, cyclin E, cdk2, E2F and RB in control of the G₁ phase of the cell cycle is described. Experimental results described with murine embryo fibroblasts (MEFs), either Rb+/+ or Rb-/-, and with the RB-deficient osteosarcoma cell line, Saos-2, served as the basis for the formulation of this mathematical model. A model employing the known interactions of these six proteins does not reproduce the experimental observations described in the MEFs. The appropriate modelling of G₁ requires the inclusion of a sensing mechanism which adjusts the activity of cyclin E/cdk2 in response to both RB concentration and growth factors. Incorporation of this sensing mechanism into the model allows it to reproduce most of the experimental results observed in Saos-2 cells, Rb-/- MEFS, and Rb+/+ MEFs. The model also makes specific predictions which have not been tested experimentally.

Original language	English (US)
Pages (from-to)	171-194
Number of pages	24
Journal	Cell Proliferation
Volume	30
Issue number	3-4
DOIs	https://doi.org/10.1111/j.1365-2184.1997.tb00933.x
State	Published - 1997

ASJC Scopus subject areas

Cell Biology

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10.1111/j.1365-2184.1997.tb00933.x

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abstract = "A mathematical model integrating the roles of cyclin D, cdk4, cyclin E, cdk2, E2F and RB in control of the G1 phase of the cell cycle is described. Experimental results described with murine embryo fibroblasts (MEFs), either Rb+/+ or Rb-/-, and with the RB-deficient osteosarcoma cell line, Saos-2, served as the basis for the formulation of this mathematical model. A model employing the known interactions of these six proteins does not reproduce the experimental observations described in the MEFs. The appropriate modelling of G1 requires the inclusion of a sensing mechanism which adjusts the activity of cyclin E/cdk2 in response to both RB concentration and growth factors. Incorporation of this sensing mechanism into the model allows it to reproduce most of the experimental results observed in Saos-2 cells, Rb-/- MEFS, and Rb+/+ MEFs. The model also makes specific predictions which have not been tested experimentally.",

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AU - Zimmerman, S. O.

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A mathematical model of the regulation of the G₁ phase of Rb+/+ and Rb-/- mouse embryonic fibroblasts and an osteosarcoma cell line

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