We have investigated the role of endogenous retroviral mink cell focus-forming (MCF) genes in the regulation of mouse bone marrow hemopoietic progenitor cell proliferation. The p15E protein coded by the MCF env gene is expressed by early hemopoietic progenitors, mostly on spleen colony forming units (CFUs-12) and on erythropoietin-independent erythroid progenitors. Stimulation of cell proliferation in hemopoietic precursors by steroid hormone (testosterone propionate) treatment resulted in upregulation of the expression of the endogenous p15E protein on bone marrow cells. Blocking of endogenous retroviral MCF env gene expression on the activated hemopoietic progenitors by antisense oligonucleotides inhibited their proliferation. These data suggest that the endogenous MCF env genes act as growth-regulators for pluripotent hemopoietic progenitors.

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