FAILURE TO DEPHOSPHORYLATE RETINOBLASTOMA PROTEIN IN DRUG-RESISTANT CELLS

Hypophosphorylation of retinoblastoma protein (RB) accompanies the DNA damage-induced, p53-independent G(1) arrest and apoptosis in two p53- null human leukemic cell lines, HL-60 and U937 (Q. P. Dou et al., Proc . Natl. Acad. Sci. USA, 92: 9019-9023, 1995). When an HL-60 cell line resistant to cytosine arabinoside was exposed to this DNA-damaging age nt, neither RE hypophosphorylation nor apoptosis were observed. In con trast, treatment of these cells with another DNA-damaging agent, etopo side, dramatically induced these events, which were inhibitable by the addition of zinc chloride, a protein tyrosine phosphatase inhibitor. Induction of hypophosphorylation of RE may be an important novel strat egy for treating drug-resistant cancers.