This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Shelly, C. Articles by Herrera, R. Search for Related Content PubMed PubMed Citation Articles by Shelly, C. Articles by Herrera, R.

K562 Cells Resistant to Phorbol 12-Myristate 13-acetate-induced Growth Arrest: Dissociation of Mitogen-activated Protein Kinase Activation and Egr-1 Expression from Megakaryocyte Differentiation¹

Department of Cell Biology, Parke-Davis Pharmaceutical Research Division of Warner-Lambert Company, Ann Arbor, Michigan 48105 [C. S., R. H.], and Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan and Veteran’s Affairs Medical Center, Ann Arbor, Michigan 48109 [L. P.]

Abstract

The K562 cell line undergoes megakaryocytic differentiation in response to phorbol 12-myristate 13-acetate (PMA) stimulation. This event correlates with mitogen-activated protein kinase activation, cell cycle arrest, and expression of the Egr-1 transcription factor. We have isolated K562 cells that are resistant to the growth-inhibitory action of PMA. Molecular characterization demonstrates that PMA resistance is downstream from PMA-induced activation of the mitogen-activated protein kinase pathway. Although the levels of Egr-1 expression and cyclic AMP-responsive element-binding protein phosphorylation are comparable in wild-type and PMA-resistant clones in response to PMA, the expression of megakaryocytic cell surface marker CD41 is detected only in the wild-type cells. The lack of differentiation of the PMA-resistant clones correlates with a failure of the PMA-treated cells to induce dephosphorylation and down-regulation of the retinoblastoma protein. These cells may provide a useful model system to distinguish those events that are connected to cell cycle arrest from those involved in the differentiation program initiated by PMA.