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Volume 7, Issue 6 (Suppl) J Gastrointest Dig Syst, an open access journal
ISSN: 2161-069X
Page 27
December 07-08, 2017 Madrid, Spain
&
13th International Conference on Clinical Gastroenterology & Hepatology
2nd International Conference on Digestive Diseases
CO-ORGANIZED EVENT
Characterization of novel mouse model of gastrointestinal cancer
Yonghua Bao1, Yongchen Guo1 and Wancai Yang1,2
1Jining Medical University, China
2University of Illinois at Chicago, USA
C olorectal cancer (CRC) is one of the most common cancers and a leading cause of cancer-related death in worldwide.
Several decades effort have revealed that the development and progression of colorectal cancer is linked to the oncogenic
signaling activation, particularly, the activation of Wnt/β-catenin or chronic colitis-associated inflammatory signaling, etc.
We have found that PRSS8 was significantly reduced in esophageal and colorectal cancers and acted as a tumor suppressor
in colitis-associated colorectal cancer through targeting Sphk1/Stat3/Akt signaling pathway. To determine the roles of PRSS8
in colorectal cancer in vivo, we developed a conditional knockout mouse model - Intestine-specific deletion of Prss8 in mice
(Prss8 fl/fl-Cre+, Prss8 CKO), and found that PRSS8 deletion caused spontaneous formation of colitis and intestinal tumors.
At the age of about 3 months, about 20% of the Prss8 CKO mice exhibited inflamed rectum and then exerted rectal prolapse.
Histopathologic analysis showed that 60% Prss8 CKOmice had developed chronic inflammation in large intestine at 3 months.
Interestingly, 45% Prss8 CKO mice had developed hyperplasia in small intestine at 3 months. At the age of 6 months, 80% of
the Prss8 CKO mice developed adenomas, and at the age of nine months, 100% of the Prss8 CKO mice developed adenomas.
Further studies showed that gastrointestinal tumorigenesis was linked to the Disruption of intestinal epithelial cell maturation:
more proliferative cells and moved faster in the Prss 8 CKO mouse, assayed by BrdU staining and migration assay. Moreover,
Prss 8 CKO mouse intestine exhibited less mature mucin drops and goblet cells at the crypts of small and large intestine in
comparison with the WT mice. Gene profile using mouse intestinal epithelial cells and gene set enrichment analysis showed
that the tumorigenesis was associated with oncogenic signaling pathways, including Wnt/beta-catenin and inflammatory
signaling. The underlying mechanisms are under further investigation.
Biography
Yonghua Bao has completed her graduation from Jiamusi Medical University, China with a Clinical Medicine background, PhD in Biochemistry and Molecular
Biology from Jilin University and Post-doctoral training in Biochemistry and Molecular Biology at the State Key Laboratory of China Agricultural University.
Yonghua Bao et al., J Gastrointest Dig Syst 2017, 7:6(Suppl)
DOI: 10.4172/2161-069X-C1-058