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Publications (2)3.99 Total impact

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    Article: EBV-positive Hodgkin lymphoma is associated with suppression of p21cip1/waf1 and a worse prognosis.
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    ABSTRACT: About 30-50% of Hodgkin lymphomas (HLs) harbor the Epstein-Barr virus (EBV), but the impact of EBV infection on clinical outcomes has been unclear. EBV-encoded small RNAs (EBERs) are presented in all EBV-infected cells, but their functions are still less understood. EBER1 was transfected into two HL cell lines, KMH2 and L428, and microarrays were used to screen for EBER1-induced changes. We found that EBER1 suppressed p21cip1/waf1 transcription in HL cell lines. In addition, positive regulators of p21cip1/waf1 transcription, such as p53, EGR1, and STAT1, were decreased. Suppression of p21cip1/waf1 in the EBER1+ HL cell lines was associated with increased resistance to histone deacetylase inhibitors or proteasome inhibitors, drugs known to cause apoptosis by increasing p21cip1/waf1 levels. On biopsy specimens, EBV+ HLs had weaker expression of both p21cip1/waf1 and active caspase 3. Clinically, suppression of p21cip1/waf1 in EBV+ HLs was associated with a worse 2-year disease-free survival rate (45% for EBV+ HLs vs. 77% for EBV- HLs, p = 0.002). Although the underlying mechanisms are still relatively unclear, EBER1 inhibits p21cip1/waf1 transcription and prevents apoptosis through down-regulation of p53, EGR1, and STAT1. The anti-apoptotic activity of EBER1 may be important in the rescue of Reed-Sternberg cells from drug-induced apoptosis and in the clinical behaviors of EBV+ HLs.
    Molecular Cancer 02/2010; 9:32. · 3.99 Impact Factor
  • Article: EBV-positive Hodgkin lymphoma is associated with suppression of p21<sup>cip1/waf1 </sup>and a worse prognosis
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    ABSTRACT: Abstract Background About 30-50% of Hodgkin lymphomas (HLs) harbor the Epstein-Barr virus (EBV), but the impact of EBV infection on clinical outcomes has been unclear. EBV-encoded small RNAs ( EBER s) are presented in all EBV-infected cells, but their functions are still less understood. Results EBER1 was transfected into two HL cell lines, KMH2 and L428, and microarrays were used to screen for EBER1 -induced changes. We found that EBER1 suppressed p21 <sup>cip1/waf1 </sup>transcription in HL cell lines. In addition, positive regulators of p21 <sup>cip1/waf1 </sup>transcription, such as p53, EGR1, and STAT1, were decreased. Suppression of p21 <sup>cip1/waf1 </sup>in the EBER1 <sup>+ </sup>HL cell lines was associated with increased resistance to histone deacetylase inhibitors or proteasome inhibitors, drugs known to cause apoptosis by increasing p21<sup>cip1/waf1 </sup>levels. On biopsy specimens, EBV<sup>+ </sup>HLs had weaker expression of both p21<sup>cip1/waf1 </sup>and active caspase 3. Clinically, suppression of p21<sup>cip1/waf1 </sup>in EBV<sup>+ </sup>HLs was associated with a worse 2-year disease-free survival rate (45% for EBV<sup>+ </sup>HLs vs . 77% for EBV<sup>- </sup>HLs, p = 0.002). Conclusion Although the underlying mechanisms are still relatively unclear, EBER1 inhibits p21 <sup>cip1/waf1 </sup>transcription and prevents apoptosis through down-regulation of p53, EGR1, and STAT1. The anti-apoptotic activity of EBER1 may be important in the rescue of Reed-Sternberg cells from drug-induced apoptosis and in the clinical behaviors of EBV<sup>+ </sup>HLs.
    Molecular Cancer. 01/2010;