Failure to dephosphorylate retinoblastoma protein in drug-resistant cells

Abstract

Hypophosphorylation of retinoblastoma protein (RB) accompanies the DNA damage-induced, p53-independent G1 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 agent, neither RB hypophosphorylation nor apoptosis were observed. In contrast, treatment of these cells with another DNA-damaging agent, etoposide, dramatically induced these events, which were inhibitable by the addition of zinc chloride, a protein tyrosine phosphatase inhibitor. Induction of hypophosphorylation of RB may be an important novel strategy for treating drug-resistant cancers.