PT  - JOURNAL ARTICLE
AU  - Mei-Chih Wang
AU  - Jin Huang Liu
AU  - Fung-Fang Wang
TI  - Protein Tyrosine Phosphatase-Dependent Activation of β-Globin and δ-Aminolevulinic Acid Synthase Genes in the Camptothecin-Induced IW32 Erythroleukemia Cell Differentiation
AID  - 10.1124/mol.51.4.558
DP  - 1997 Apr 01
TA  - Molecular Pharmacology
PG  - 558--566
VI  - 51
IP  - 4
4099  - http://molpharm.aspetjournals.org/content/51/4/558.short
4100  - http://molpharm.aspetjournals.org/content/51/4/558.full
SO  - Mol Pharmacol1997 Apr 01; 51
AB  - Camptothecin, an antitumor drug that specifically targets topoisomerase I, induced IW32 erythroleukemia cells to differentiate along the erythroid pathway, as demonstrated by the increased mRNA and protein expression of hemoglobin. Unlike other chemically induced erythroleukemia cell differentiation, no c-myc mRNA down-regulation was observed in the early phases of drug treatment. Among the heme-synthesizing enzyme mRNAs that were analyzed, only that of the erythroid-specific δ-aminolevulinic acid synthase (ALAS-E) was stimulated. Vanadate or benzylphosphonic acid, which inhibited protein tyrosine phosphatases (PTPase), blocked the camptothecin-induced differentiation. Maximal inhibition was attained if vanadate was added within the first 6 hr of camptothecin treatment, after which vanadate gradually lost its effectiveness. Camptothecin-induced expression of β-globin or ALAS-E transcript levels was inhibited in the presence of cycloheximide or vanadate. It was also shown that vanadate blocked differentiation of IW32 cells induced by sodium butyrate, VM-26, and p53. Increased PTPase activity could be observed 48 hr after cells were treated with camptothecin, VM-26, or sodium butyrate. Analysis of PTPase activity in the course of camptothecin treatment showed elevated levels of PTPase in the cytosol and the nucleus, with a greater increase demonstrated in the cytosol than in the nucleus. Our results suggest that by stimulating the β-globin and ALAS-E gene expression, PTPase plays a critical role in the induced differentiation of IW32 erythroleukemia cells.