Aggressive tumor growth of human TUR leukemia cells is associated with high levels of c-myc expression and down-regulation of p20-max

A sub-clone of human U937 myeloid-leukemia cells, termed TUR, was investigated with respect to its proliferative capacity in vivo and in vitro, Karyotypic analysis demonstrated certain differences in TUR cells and some monocytic properties, such as expression of alpha-naphthyl acetate esterase, were constitutively higher in TUR cells than in U937 cells. However, stimulation of both cell lines by the differentiation-inducing phorbol ester TPA revealed reduced responsiveness of TUR cells in the expression of cu-naphthyl acetate esterase and the generation of O-2(-)-anions as compared with U937 cells. Injection into scid mice resulted in potent and rapid tumor development of TUR cells: while 87% of U937-cell injections resulted in tumors after about 14 days, 100% of TUR cell injections produced a tumor after only 11 days, with a tumor area approximately 3.1-times larger than tumors generated by U937 cells, In this context, Western-blot analysis of the myc family revealed high levels of c-myc protein accumulation in TUR cells even in the presence of TPA. In contrast, incubation of U937 cells with phorbol ester was associated with progressive down-regulation of c-myc protein, c-myc can also form transcriptionally active heterodimeric complexes with the nuclear phosphoproteins p20/p22 max: thus, TPA treatment resulted in down-regulation of the p20 form of max in TUR cells. Another regulatory factor in the myc family, mad-1 was expressed unaltered in U937 and in TUR cells regardless of TPA stimulation. (C) 1997 Wiley-Liss, Inc.