PT  - JOURNAL ARTICLE
AU  - Mohapatra, Subhra
AU  - Chu, Baoky
AU  - Wei, Sheng
AU  - Djeu, Julie
AU  - Epling-Burnette, P. K.
AU  - Loughran, Thomas
AU  - Jove, Richard
AU  - Pledger, W. Jackson
TI  - Roscovitine Inhibits STAT5 Activity and Induces Apoptosis in the Human Leukemia Virus Type 1-Transformed Cell Line MT-2
DP  - 2003 Dec 01
TA  - Cancer Research
PG  - 8523--8530
VI  - 63
IP  - 23
4099  - http://cancerres.aacrjournals.org/content/63/23/8523.short
4100  - http://cancerres.aacrjournals.org/content/63/23/8523.full
SO  - Cancer Res2003 Dec 01; 63
AB  - T cells expressing human leukemia virus (HTLV) type 1, the etiological agent of adult T-cell leukemia, are remarkably resistant to conventional chemotherapy, and the need for drugs that effectively kill these cells is apparent. Here we show that roscovitine, an inhibitor of cyclin-dependent kinases (CDKs), induces the apoptosis of the HTLV-1-transformed T-cell line MT-2. Roscovitine prevented the tyrosine phosphorylation and consequent activation of the transcription factor signal transducer and activator of transcription (STAT) 5 when presented to MT-2 cells in the presence or absence of a caspase-3 inhibitor, and ectopic expression of a dominant-negative form of STAT5 in MT-2 cells induced apoptosis. Roscovitine and dominant-negative STAT5 also reduced the expression of the antiapoptotic protein XIAP, and STAT5 was associated with the XIAP promoter in vivo. Antibody to platelet-derived growth factor (PDGF) α receptors coprecipitated STAT5 from extracts of untreated but not roscovitine-treated cells. The tyrosine phosphatase inhibitor sodium orthovanadate ablated the inhibitory effects of roscovitine on STAT5/PDGF α receptor interaction, STAT5 activity, and cell survival. We suggest that roscovitine reduces the abundance of tyrosine-phosphorylated PDGF α receptors; as a result, STAT5 does not become active, and STAT5 gene products required for cell survival are not expressed. ©2003 American Association for Cancer Research.