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Stat3 activation in human endometrial and cervical cancers
C-L Chen1, F-C Hsieh, J C Lieblein
1Center for Childhood Cancer, Columbus Children's Research Institute, Columbus, OH 43205, USA.
British Journal of Cancer
|February 22, 2007
Summary
Signal transducer and activator of transcription 3 (Stat3) is activated in endometrial and cervical cancers. Inhibiting Stat3 signaling offers a promising therapeutic target for these cancers.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genetics
Background:
- Signal transducer and activator of transcription 3 (Stat3) is a proto-oncogene implicated in cancer development.
- Constitutive Stat3 activation is observed in various human cancers, but its role in endometrial and cervical cancers is unexplored.
Purpose of the Study:
- To investigate the activation status of Stat3 in human endometrial and cervical cancers.
- To explore Stat3 as a potential therapeutic target in these malignancies.
Main Methods:
- Examined tyrosine phosphorylation of Stat3 in endometrial and cervical cancer tissues and cell lines using tissue microarrays.
- Utilized immunohistochemical staining to assess Stat3 activation and downstream gene expression.
- Employed adenovirus-mediated gene transfer of a dominant-negative Stat3 mutant and a JAK/Stat3 inhibitor (JSI-124) to evaluate therapeutic efficacy.
Main Results:
- Elevated Stat3 phosphorylation was detected in both endometrial and cervical cancer cell lines and patient specimens.
- Activated Stat3 correlated with increased expression of antiapoptotic genes (Bcl-xL, survivin, Mcl-1).
- Inhibition of Stat3 signaling via gene transfer or a small molecule inhibitor induced apoptosis and suppressed cell growth in cancer cell lines.
Conclusions:
- Stat3 is constitutively activated in human endometrial and cervical cancers.
- Targeting Stat3 signaling represents a potential therapeutic strategy for endometrial and cervical cancer intervention.
