This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend 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 HighWire Citing Articles via Google Scholar Google Scholar Articles by Dou, Q. P. Articles by Lui, V. W. Y. Search for Related Content PubMed PubMed Citation Articles by Dou, Q. P. Articles by Lui, V. W. Y.

Failure to Dephosphorylate Retinoblastoma Protein in Drug-resistant Cells¹

Department of Pharmacology, University of Pittsburgh School of Medicine, and Experimental Therapeutics Program, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, 15213-2582

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.

¹ Supported by a start-up fund from the Department of Pharmacology, University of Pittsburgh School of Medicine (to Q.P.D.).

² To whom requests for reprints should be addressed, at Department of Pharmacology, University of Pittsburgh School of Medicine, W952 Biomedical Science Tower, 200 Lothrop Street, Pittsburgh, PA 15213-2582.

Received 9/19/95. Accepted 10/ 5/95.

This article has been cited by other articles:

				M. Wallace and K. L. Ball Docking-Dependent Regulation of the Rb Tumor Suppressor Protein by Cdk4 Mol. Cell. Biol., June 15, 2004; 24(12): 5606 - 5619. [Abstract] [Full Text] [PDF]

				R. P. Santini, S. Myrand, C. Elferink, and J. J. Reiners Jr. Regulation of Cyp1a1 Induction by Dioxin as a Function of Cell Cycle Phase J. Pharmacol. Exp. Ther., November 1, 2001; 299(2): 718 - 728. [Abstract] [Full Text] [PDF]

				Z. Wang, G. Van Tuyle, D. Conrad, P. B. Fisher, P. Dent, and S. Grant Dysregulation of the Cyclin-dependent Kinase Inhibitor p21 WAF1/CIP1/MDA6 Increases the Susceptibility of Human Leukemia Cells (U937) to 1-{beta}-D-Arabinofuranosylcytosine-mediated Mitochondrial Dysfunction and Apoptosis Cancer Res., March 1, 1999; 59(6): 1259 - 1267. [Abstract] [Full Text] [PDF]

				S. J. Morana, C. M. Wolf, J. Li, J. E. Reynolds, M. K. Brown, and A. Eastman The Involvement of Protein Phosphatases in the Activation of ICE/CED-3 Protease, Intracellular Acidification, DNA Digestion, and Apoptosis J. Biol. Chem., July 26, 1996; 271(30): 18263 - 18271. [Abstract] [Full Text] [PDF]