ICMI 2015

T.41 Critical Role for Signal Transducer and Activator of Transcription 6 (STAT6) during Colitis Associated Colorectal Cancer

Thursday, July 16, 2015
Grand Hall and Gallery, Ground Floor & 1st Floor (Maritim Hotel)
Luis I Terrazas , Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autonoma de Mexico, Tlalnepantla, Mexico
Sonia León-Cabrera, PhD , Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autonoma de Mexico, Tlalnepantla, Mexico
Miriam Rodriguez-Sosa, PhD , UNAM, FES Iztacala. UBIMED., Tlalnepantla, Mexico
Yadira Ledesma-Soto, PhD , Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autonoma de Mexico, Tlalnepantla, Mexico
Yael Delgado, Biol. , FES-Iztacala,UNAM, Tlalnepantla, Mexico
Emmanuel Molina , FES-Iztacala,UNAM, Tlalnepantla, Mexico
Whereas a causal association between chronic inflammation and tumor development has been well established and supported in both, animal and epidemiological studies, the role of transcription factors,  in particular those related with cytokine signaling, during colitis-associated colorectal cancer (CAC) development is almost unknown.   Here we have analyzed the pathophysiologic implication of STAT6 signaling pathway on the establishment and progression of CAC. CAC was induced in both STAT6-KO and  BALB/c (wild-type, WT) mice by injection of 12.5 mg/kg azoxymethane followed by 2% dextran sodium sulfate exposure to elicit colitis. On days 20, 40 and 68 after CAC induction, mice were sacrificed to evaluate colonic inflammation, proliferation and tumorigenesis. STAT6-KO mice did not show any bleeding or diarrhea throughout all the experiment, besides; more than 60% of these mice were free of tumor at day 68, whereas WT mice developed tumors as early as 20 days after CAC induction and by the end of the experiment 100% of these mice displayed tumors. Tumor numbers per mouse (0.8 versus 11.6), and bowel weight (0.3g versus 0.6g) were significantly decreased in STAT6-KO mice compared to WT mice. Both inflammation and proliferation scores in colon from STAT6-KO mice were significantly lower than WT mice. An intense apoptotic process early in CAC progression was recorded, as well as lower expression of COX2 and β-catenin in colonic areas of STAT6-KO mice, these data were associated with a strong mRNA expression of IFN-γ. Our data suggest a main role for STAT6 in favoring establishment and progression of CAC.