Neuronal localization of the Adenomatous polyposis coli tumor suppressor protein

Recent biochemical studies have demonstrated that the adenomatous polyposis coli gene, initially identified via its link to colon cancer, is expressed at high levels in the brain. Furthermore, the ability of this tumor suppre ssor protein to bind to Discs-Large and beta-catenin, proteins implicated i n organizing synaptic structure, point to a role for APC in neuronal signal ling. However, anatomical studies have provided conflicting results regardi ng its localization in brain. In situ hybridization studies predict neurona l expression of APC, while immunostaining studies performed with a panel of N-terminal antibodies detected staining of glial cells, especially oligode ndrocytes. In this study, we have examined the basis for this discrepancy a nd provide evidence that the glial staining pattern detected in previous st udies reflects cross-reactivity with an unrelated antigen rather than the l ocalization of APC. Furthermore, we have performed immunohistochemical stud ies with a C-terminal APC antibody which reveal a neuronal pattern of stain ing closely matching that predicted by the in situ studies. For example, in the hippocampus APC immunostaining is detected in the pyramidal neurons an d dentate granule cells, which fits well with the localization of APC mRNA. Examination of APC immunostaining in other regions revealed that particula rly intense staining was displayed by large neurons, including layer V cort ical pyramidal neurons, cerebellar Purkinje cells, and olfactory bulb mitra l cells. Within labeled neurons, APC staining was apparent in the cytoplasm , as well as in dendritic and axonal processes. To help clarify the localization of APC in brain, we have conducted additio nal in situ hybridization and immunohistochemical studies. These results pr ovide compelling evidence that APC is expressed predominantly in neurons ra ther than in glial cells as reported previously. (C) 1999 IBRO. Published b y Elsevier Science Ltd.