S2003 Decreased Expression of RAS Protein Activator Like 1 in Gastric Cancer

Abstract

moribund infant mice, and wild-type controls. Genes of interest and cell lineage markers were examined by immunohistochemistry. Results: Line 1 transgenic male pups are born and nurse but lose weight and die by 2-3 days of age. Their intestines lack normal color gradation and contain hemoccult and fat positive black fecal matter. Uniform ectopic expression of the transgene in the infant small intestine villi is associated with premature crypt formation, early sucrase-isomaltase expression, and greatly reduced lactase activity. Females have patchy transgene expression and are slightly, but significantly, smaller than wild-type females at weaning. Flag-tag positive villi arise from crypts that lack lysozyme positive paneth cells and, as previously reported, have expanded goblet cell size and number in adult mice. Line 5 transgenic pups of both sexes are runted and few survive to weaning. Dying pups have features similar to line 1. Loss of paneth cells and expanded goblet cells also occur with high transgenic expression. Pups are normal sized in line 4 that has very patchy transgene expression, and in line 6 that has extensive but lower expression levels of VillinCdx2. Paneth cell loss occurs in line 4 crypts with two adjacent Flag positive villi, but are retained in line 6. Conclusions: High over-expression of Cdx2 in the small intestine is associated with decreased postnatal growth and high mortality. Over-expression of Cdx2 during embryogenesis promotes epithelial maturation with early crypt development, enhanced sucrase-isomaltase, and diminished lactase expression. Moreover, the level of Cdx2 expression can direct differentiation toward the goblet cell and away from the paneth cell lineages. We conclude that Cdx2 expression plays important roles directing intestinal epithelial maturation, differentiation, and lineage selection in addition to effects on gene expression, cell adhesion, and cell proliferation.