TNF-α, IL-6, and Phorbol Ester but Not G-, M-, GM-CSF, IL-3, and IL-4, Induce Monocytic Differentiation and Modulate Expression of c-fos, c-fms, and c-myc in the Human Monoblast Line THP-1

Abstract

Oncogenes are known to play a central role in the transformation, unrestricted proliferation, and aberrant differentiation of the tumor cell [2]. In this regard the proto-oncogenes c-myc, c-fos, and c-fms, have been extensively analyzed. Both c-fos and c-myc encode for nuclear proteins, whereas the c-fms product represents a transmembrane glycoprotein associated with tyrosine kinase activity, identical to the receptor for the monocyte colony stimulating factor (M-CSF) [4, 14]. The c-fos protein is thought to activate in synergy with c-jun the transcription activation factor AP-1, shown to induce cellular transformation [8, 15]. A functional role of the c-fos protein during monocytic differentiation has also been shown [2, 9, 12]. Furthermore, the c-fos protein has been described to be involved in down-regulatory processes of the transcriptional activity after mitogenic stimulation [15]. The function of c-myc is poorly understood. The c-myc- encoded protein seems to interact with DNA and thus to control cell cycle progression [4, 7]. Down-regulation of c-myc has been shown to be associated with inhibition of proliferation and induction of differentiation [5, 12]. Similar to c-fos, the cellular expression of c-fms is associated with hematopoietic maturation along the monocytic lineage [13, 14].