Stat3 activation in prostatic carcinomas.
BACKGROUND
Activated Stat3 is found in various types of immortal cell lines and cancers. We and others have previously demonstrated that Stat3 is constitutively activated in rat and human prostate cancer cell lines, and that Stat3 activation is involved in IL-6-mediated signaling transduction in prostate cancer cells. The aim of this study is to examine quantitative Stat3 activity in benign and malignant human prostate tissues and analyze the association between Stat3 activity levels and the clinical and pathologic parameters.


METHODS
Stat3 activity levels were analyzed in a total of 104 human primary prostate tissues using electromobility shift assay and immunohistochemical staining for phosphorylated Stat3. The tissue samples used were 42 prostate carcinomas, 42 matched normal prostate tissues from patients with prostatic adenocarcinoma (normal adjacent to tumor), and 20 normal prostate tissues from organ donors.


RESULTS
Significantly higher levels of constitutive Stat3 activity were detected in both prostate carcinomas and the matched normal prostate tissues adjacent to tumors compared to the normal prostates from donors without prostate cancer. There was no significant difference of Stat3 activity in foci of tumor and normal prostate tissue adjacent to tumor. No correlation was seen between Stat3 activity and Gleason grade or serum PSA levels in samples from prostate carcinomas.


CONCLUSIONS
These results indicate that Stat3 is constitutively activated in prostate cancer. The high level of Stat3 activity in both the prostate carcinomas and the normal prostate tissues adjacent to tumors suggests that Stat3 activation may occur before detectable histological alterations of the prostate.
Dhir
Rajiv
R
Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
Ni
Zuyao
Z
Lou
Wei
W
DeMiguel
Fernando
F
Grandis
Jennifer Rubin
JR
Gao
Allen C
AC
D002471:Cell Transformation, Neoplastic; D004268:DNA-Binding Proteins / Q000032:analysis / Q000096:biosynthesis*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009367:Neoplasm Staging; D011467:Prostate / Q000502:physiology; D011471:Prostatic Neoplasms / Q000473:pathology*; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000032:analysis / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators