Important note: Information in this article was accurate in 1994. The state of the art may have changed since the publication date.
Friend virus-transformed cells express hemoglobin and become responsive to erythropoietin upon expression of p53 protein (Meeting abstract).
6th p53 Workshop. November 1-5, 1992, Tiberias, Israel, p. 38, 1992.. Unique Identifier : AIDSLINE ICDB/94698122 Johnson P; Chung S; Benchimol S; Dept. of Medical Biophysics, Ontario Cancer Inst., Univ. of; Toronto, Toronto, Ontario, Canada
Abstract:
The murine allele ts p53val135 encodes a temperature-sensitive p53 protein that behaves as a mutant polypeptide at 37 C and as a wild type polypeptide at 32 C. We have stably introduced this ts allele into the p53 nonproducer, Friend erythroleukemia cell line DP16-1. This cell line was derived from a mouse infected with the polycythemia strain of Friend virus and like other erythroleukemia cell lines transformed by this virus, grows independently of erythropoietin due to expression of the viral env gp55 protein which binds to and activates the erythropoietin receptor. When incubated at 32 C, DP16-1 cells expressing ts p53val135 protein arrested in the G1/G0-phase of cell cycle, rapidly lost viability and expressed hemoglobin, a marker of erythroid differentiation. Erythropoietin had a striking effect on p53val135-expressing cells at 32 C by prolonging their survival and diminishing the extent of hemoglobin production. This response to erythropoietin was not accompanied by downregulation of viral gp55 protein. In the clonogenic assays that have been developed to examine hemopoietic precursors, erythropoietin is a necessary component for the development of erythroid colonies. Erythroid colonies result from cells undergoing proliferation and differentiation, and so it has been difficult to assign a specific role to erythropoietin in this process. Our data indicate that erythropoietin prolongs the survival of Friend cells expressing wild-type p53 protein and argues against a role for erythropoietin in initiating the differentiation process in Friend cells.
Keywords: Animal Cell Cycle Cell Transformation, Neoplastic Cell Transformation, Viral Down-Regulation (Physiology) Erythropoietin/*METABOLISM Friend Virus/*PATHOGENICITY Gene Products, env/METABOLISM Hemoglobins/*METABOLISM Leukemia, Erythroblastic, Acute/*METABOLISM Mice Protein p53/GENETICS/*METABOLISM Tumor Cells, Cultured ABSTRACT 940530
M9450903
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