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Differential Expression of ras Protooncogenes during in Vitro Differentiation of Human Erythroleukemia Cells¹

Departamento de Biologia Molecular y Centro Mixto de Estudios Avanzados de Biologia Molecular, CSIC, Universidad de Cantabria [M. D. D., A. F. Q., M. T. G-C., C. A. M., J. L.], and Servicio de Hematologia, Hospital Universitario Marqués de Valdecilla [M. A. C., C. R.], 39011 Santander, Spain

We have compared the expression of the ras protooncogene family (H-, K-, and N-ras) in leukemia cell differentiation utilizing as a model K562 and HEL erythroleukemia cells treated either with 1-ß-arabinofuranosylcytosine or 12-O-tetradecanoylphorbol-13-acetate (TPA). 1-ß-D-Arabinofuranosylcytosine induced terminal erythroid differentiation of K562 cells, while TPA induced myeloid differentiation of K562 and HEL cells, resulting in myelomonocytic-like cells expressing macrophagic and megakaryocytic markers. H-ras mRNA levels showed a dramatic decrease in K562 cells subjected to erythroid and myelomonocytic differentiation. The same result was found at the protein level for p21^H-ras. Expression of K-ras and N-ras in K562 cells also decreased with differentiation, although significant mRNA levels remained despite cessation of cell proliferation. The decrease in K-ras expression was greater for TPA-treated cells than for 1-ß-arabinofuranosylcytosinetreated cells. TPA-induced myelomonocytic differentiation in HEL cells also resulted in a dramatic down-regulation of H-ras mRNA levels. Thus, by using a leukemia cell line able to differentiate along two different lineages, our results reveal a lineage-specific modulation of ras gene family expression.

¹ Supported by Grant SAL90/0666 from CICYT. C. A. M. is a recipient of an ICI fellowship from the Spanish government. A. F. Q. and M. T. G. are recipients of PFPI fellowships from the Ministerio de Educación y Ciencia.

² To whom requests for reprints should be addressed, at Departamento de Biologia Molecular, Facultad de Medicina, Av. del Cardenal Herrera Oria s/n, 39011 Santander, Spain.

Received 4/13/92. Accepted 8/21/92.

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