Regulation of PSCA expression by m‐Numb in the stomach (904.2)

Abstract

Prostate stem cell antigen (PSCA) is a GPI‐anchored cell surface protein expressed in the normal epithelium of several tissues including the isthmus region of the gastric mucosa. Recently, a genome‐wide association study revealed several SNPs in the PSCA‐gene to be associated with gastric cancer and duodenal ulcer risk. However, the underlying regulatory mechanisms of PSCA are still unclear.Methods: Msi1‐KO mice with lowered expression of m‐Numb in the stomach and wild‐type ICR mice were used for in vivo studies. In vitro studies were carried out with the mouse gastric epithelial cell line MGE507. Overexpression and suppression of m‐Numb in MGE507 cells was achieved by transfection with lentiviral particles carrying an m‐Numb expression vector and shRNA expression vector, respectively. Gene expression was analysed with qRT‐PCR, and western blotting was used to measure protein levels.Results: In Msi1‐KO mice, a significantly reduced expression‐ and protein level of PSCA was found when comparing the gastric mucosa to wild‐type ICR mice. Expectedly, the protein level of m‐Numb was also verified as lower in the KO‐line. Silencing m‐Numb expression in MGE507 cells resulted in a reduction in protein level of PSCA, and overexpression of m‐Numb led to an increased PSCA‐level.Conclusion: PSCA gene expression and protein level was regulated by m‐Numb in the mouse stomach and in mouse gastric epithelial cells.