ETS-1 INDUCES INCREASED EXPRESSION OF ERYTHROID MARKERS IN THE PLURIPOTENT ERYTHROLEUKEMIC CELL-LINES K562 AND HEL

Members of the ETS gene family are known to be expressed in hematopoie tic tissues and cell lines, and there is increasing evidence that ETS proteins may play a role in normal hematopoietic cell development. We demonstrate that ETS-1 can contribute to the development of an erythro id phenotype in vitro. The pluripotent erythroleukemic K562 and HEL ce ll lines express messages for a number of ETS genes, but only c-ETS-1 levels are elevated in response to treatment with hemin or cytosine ar abinofuranoside (Ara-C), agents which induce erythroid differentiation . Furthermore, ETS-1 antisense oligonucleotides inhibit hemoglobinizat ion of cells treated with Ara-C or hemin, and K562 and HEL cells infec ted with retrovirus expressing the c-ETS-1 gene exhibit a significant increase in erythroid character (as indicated by benzidine staining fo r hemoglobin (Hb) and surface marker analysis), a dramatic increase in responsiveness to hemin or Ara-C, and a decreased rate of proliferati on (20-40% of control rates). In contrast, infection with virus expres sing ETS-2 or vector sequences only causes no detectable changes in th e proliferation or erythroid character of either the HEL or K562 cell lines. These data indicate a role for ETS-1 in erythroid differentiati on.