Protein 4.1B in mouse islets of Langerhans and beta-cell tumorigenesis.

Protein 4.1 family proteins are thought to interact with membrane proteins and membrane skeletons. Immunohistochemical studies by light and electron microscopy were performed on mouse pancreas with a specific antibody against protein 4.1B. Specific protein 4.1B immunolabeling was observed on endocrine cells in the islets of Langerhans. Protein 4.1B localized along the plasma membranes facing adjacent cells. By immunoelectron microscopy, the immunolabeling of the cells was restricted to the cytoplasmic side just beneath their plasma membrane, including the membranes adjacent to neighboring cells, while the plasma membranes facing endothelial cells were not immunolabeled for protein 4.1B. The immunolocalization of E-cadherin was similar, if not identical, to that of protein 4.1B supporting the idea that protein 4.1B may be functionally interconnected with adhesion molecules. In a transgenic mouse model of pancreatic beta-cell carcinogenesis (Rip1Tag2), the loss of protein 4.1B expression coincided with the phenotypic transition from adenoma to carcinoma. Therefore, we propose a role of protein 4.1B as a connecting and/or signaling molecule between membrane architecture, cell adhesion, and tumor cell invasion in mouse pancreatic endocrine cells.