Differential expression of tumor-associated genes and altered gut microbiome with decreased Akkermansia muciniphila confer a tumor-preventive microenvironment in intestinal epithelial Pten-deficient mice

Publication date: Available online 4 October 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Cody Howe, Su Jin Kim, Jonathon Mitchell, Eunok Im, Yong Sung Kim, You Sun Kim, Sang Hoon RheeAbstractPhosphatase and tensin homolog (Pten) antagonizes PI3K-Akt signaling; therefore, Pten impairment causes tumorigenesis. However, the correlation between Pten deficiency and colon cancer has remained elusive due to numerous opposite observations. To study this correlation, we examined whether Pten deficiency in intestinal epithelial cells (IECs) induces tumorigenesis.With mucosal biopsies of human colon cancer and normal colon, Pten mRNA was evaluated by quantitative PCR. Using IEC-specific Pten knockout mice (PtenΔIEC/ΔIEC), we examined the mitotic activity of IECs; and PtenΔIEC/ΔIEC; Apcmin/+ mice were generated by combining PtenΔIEC/ΔIEC with Apcmin/+ mice. Tumor-associated gene was evaluated by micro-array analysis. Fecal microbiome was analyzed through 16S rRNA gene sequencing.We found that Pten mRNA level was reduced in human colon cancer relative to normal tissues. Augmented chromatids, increased Ki-67 and PCNA expression, and enhanced Akt activation were identified in IECs of PtenΔIEC/ΔIEC mice compared to Pten+/+ littermate. Combining PtenΔIEC/ΔIEC with Apcmin/+ condition caused rapid and aggressive intestinal tumorigenesis. However, PtenΔIEC/ΔIEC mice did not develop any tumors. While maintaining the tumor-driving potential, t...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - Category: Molecular Biology Source Type: research