Unregulated Expression of the Erythropoietin Receptor Gene Caused by Insertion of Spleen Focus-Forming Virus Long Terminal Repeat in a Murine Erythroleukemia Cell Line

Autor: Masabumi Shibuya, Akihiro Tojo, H Morii, F Takaku, Y Misawa, Masayuki Hino
Rok vydání: 1991
Předmět:
Zdroj: Molecular and Cellular Biology. 11:5527-5533
ISSN: 1098-5549
DOI: 10.1128/mcb.11.11.5527-5533.1991
Popis: A murine erythroleukemia (MEL) cell line, F5-5, expressed 10,000 binding sites for erythropoietin (EPO) per cell, 10-fold more than was expressed by other murine erythroleukemia cell lines and normal erythroid progenitors. Northern (RNA) and Southern blot analyses revealed overexpression of mRNA for the EPO receptor (EPOR) and rearrangement of one of the EPOR gene alleles in F5-5 cells, respectively. Molecular cloning of F5-5-derived cDNA encoding EPOR revealed that the 5' noncoding region of the EPOR cDNA corresponds to the 3' long terminal repeat sequence of the polycythemic strain of Friend spleen focus-forming virus (F-SFFVP). The aberrant EPOR transcripts containing the 3' long terminal repeat sequence were mainly expressed in F5-5 cells. The same integration upstream of the EPOR gene was also observed in other subclones and the parent cell line. It is possible that overexpression of EPOR by viral promoter insertion will confer growth advantage to an F-SFFVP-infected erythroid progenitor cell, leading to positive clonal selection through further leukemogenic steps.
Databáze: OpenAIRE