Modulation of the constitutive activated STAT3 transcription factor in pancreatic cancer prevention: effects of indole-3-carbinol (I3C) and genistein.
BACKGROUND
The signal transducer and activator of transcription 3 (STAT3) is a latent transcription factor required in proliferation and differentiation. STAT3 is activated constitutively in a number of cancers.


METHODS
This study was conducted to assess the possible involvement of STAT3 activation in pancreatic cancer and the potential for this pathway as a target in chemopreventive strategy.


RESULTS
STAT3 was shown for the first time to be constitutively activated in human pancreatic carcinoma specimens but not in normal pancreatic tissues. Constitutively activated STAT3 was also found in pancreatic tumor cell lines (Panc-1 and MIA PaCa-2) which could be modulated by indole-3-carbinol (13C) and genistein. At concentrations higher than 10 microM, STAT3 constitutive activation is inhibited by both agents. Induction of apoptosis by 13C was also demonstrated.


CONCLUSIONS
Given its critical role in tumorigenesis, our results suggest that STAT3 activation provides an important and appropriate target for chemoprevention in pancreatic cancer treatment.
Lian
Jian P
JP
National Center for Toxicological Research, Jefferson, AR 72079, USA.
Word
Beverly
B
Taylor
Skeetora
S
Hammons
George J
GJ
Lyn-Cook
Beverly D
BD
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D010766:Phosphorylation; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism*
D016588:Anticarcinogenic Agents; D004268:DNA-Binding Proteins; D007211:Indoles; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; C016517:indole-3-carbinol; D019833:Genistein