Expression of A-kinase anchor protein 13 and Rho-associated coiled-coil containing protein kinase in restituted and regenerated mucosal epithelial cells following mucosal injury and colorectal cancer cells in mouse models

Abstract

We demonstrate the expression patterns of A-kinase anchor protein 13 (AKAP13), a scaffold protein that acts upstream of Rho signaling, and Rho-associated coiled-coil containing protein kinase (ROCK) 1/2 in mouse colorectal cancer and during the healing stage of mouse colitis. BALB/c mice received an intraperitoneal injection of azoxymethane at 10mg/kg, followed by two 7-day cycles of 3% dextran sulfate sodium (DSS) administered through their drinking water to induce colon cancer, or a 7-day administration of 4% DSS to induce colitis. The colorectal tissue was then analyzed for gene expression, histopathology, and immunohistochemistry. In the colorectal cancer, AKAP13 and ROCK1/2 were highly expressed in adenocarcinoma compared to the control tissue and low-grade dysplasia. In colitis, AKAP13 and ROCK1 were highly expressed in the restituted and regenerated mucosa but were only moderately expressed in the injured mucosal epithelium, compared to the normal epithelium that exhibited weak expression levels. ROCK2 was weakly expressed in these cells, consistent with the expression of AKAP13 and ROCK1. Furthermore, we found several clumps of epithelial cells expressing AKAP13 and ROCK1/2 in the lamina propria during the mucosal healing process, and these cells also expressed interleukin-6, which is a multipotential cytokine for both inflammation and healing. These data suggest that AKAP13 was expressed in relation with ROCK1/2, which probably play an overall role in both mucosal healing and tumorigenesis.