Cytoplasmic Accumulation of Glycogen Synthase Kinase-3 beta Is Associated with Aggressive Clinicopathological Features in Human Prostate Cancer


Li R., Erdamar S., Dai H., Sayeeduddin M., Frolov A., Wheeler T. M., ...Daha Fazla

ANTICANCER RESEARCH, cilt.29, sa.6, ss.2077-2081, 2009 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 29 Sayı: 6
  • Basım Tarihi: 2009
  • Dergi Adı: ANTICANCER RESEARCH
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.2077-2081
  • İstanbul Üniversitesi Adresli: Evet

Özet

Background: Activation of glycogen synthase kinase-3 (GSK-3) is involved in the regulation of cell growth, differentiation, mobility, proliferation and survival. However, its clinicopathologic significance remains unclear in prostate cancer (PCa). Materials and Methods: A tissue microarray was produced from 640 samples. Sections were immunostained with an antibody against the non-phosphorylated form of GSK-3(GSK-3 beta) and were digitized. Spearman correlation test was processed for correlations between GSK-3 and biological and clinicopathological variables. The prognostic value of GSK-3 beta was analyzed by Cox Regression model. Results: Cytoplasmic GSK-3 beta was higher in PCa than in normal prostate (mean expression index 4.55 vs. 3.50, p<0.0001). Conversely, nuclear expression was higher in normal prostate than that in PCa (3.38 vs. 2.04, p<0.0001). Cytoplasmic levels of GSK-3 beta were correlated with clinical stage (rho=0.095, p=0.0337), lymph node metastasis (rho=0.116, p=0.0096), extracapsular extension (rho=0.092, p=0.0392), and Gleason score (rho=0.167, p=0.0002). Increased cytoplasmic GSK-3 beta expression was correlated with high Ki-67 labeling index (rho=0.319, p<0.0001), low apoptotic index by TUNEL (rho=-0.118, p=0.0134), high levels of androgen receptor (rho=0.292, p<0.0001) and p-Akt (rho=0.396, p<0.0001). Patients with higher cytoplasmic levels of GSK-3 beta had a twofold risk of biochemical recurrence-free survival compared to those with lower levels of GSK-3 beta [HR 1.934 (1.020-3.667), p=0.043]. Conclusion: Cytoplasmic accumulation of GSK-3 beta is potentially associated with a pro-survival mechanism that promotes PCa development and progression.