Evidence for APOBEC3B mRNA and protein expression in oral squamous cell carcinomas

It has been demonstrated that APOBEC3B possesses cytidine deaminase activity, which is likely to result in C-to-T signature mutations. Increased expression of the APOBEC3B gene has been shown to correlate with higher incidence of such mutations in various cancer types, such as breast, bladder, lung, and head and neck carcinomas. In the current study, we used in silico methods, immunohistochemistry and qRT-PCR to detect the presence of APOBEC3B signature mutations and examine the levels and patterns of APOBEC3B expression in oral squamous cell carcinomas (OSCCs). Using the Cancer Genome Atlas (TCGA) database, we have found a high incidence of C-to-T transitions in head and neck squamous cell carcinomas (HNSCCs), of which OSCCs constitute the largest subgroup. Additionally, we compared APOBEC3B expression, at both mRNA and protein level, between OSCCs and non-cancerous samples. APOBEC3B was detected in both groups, but nuclear localization was consistent only in normal oral cells. APOBEC3B mRNA levels were clearly higher in OSCCs than in controls. These results suggest that while in normal oral cells APOBEC3B has an important nuclear function to fulfill, this activity may be hindered in a subgroup of tumor cells, due to the more prominent localization of the enzyme in the cytoplasm. © 2016 Elsevier Inc

Dynamic glucocorticoid-dependent regulation of Sgk1 expression in oligodendrocytes of adult male rat brain by acute stress and time of day

Recent studies support plasticity in adult brain white matter structure and myelination in response to various experiential factors. One possible contributor to this plasticity may be activity-dependent modulation of serum- and glucocorticoid-inducible kinase 1 (Sgk1) expression in oligodendrocytes. We examined whether Sgk1 expression in adult rat brain white matter is increased by acute stress-induced elevations in endogenous corticosterone and whether it fluctuates with diurnal variations in corticosterone. We observed rapid increases (within 30 min) in Sgk1 mRNA in the corpus callosum in response to acute stress, as well as large increases at the beginning of the rat's active period (the time of peak corticosterone secretion). These increases were absent in adrenalectomized rats. Corticosterone treatment of adrenalectomized rats also rapidly increased corpus callosum Sgk1 mRNA. The majority of Sgk1 mRNA in corpus callosum was co-localized with myelin basic protein mRNA, suggesting that mature oligodendrocytes respond dynamically to acute stress and circadian rhythms. The regulation of Sgk1 expression by acute stress and time of day was selective for white matter, with limited alteration of Sgk1 expression by these factors in hippocampus and somatosensory cortex. These results indicate a unique sensitivity of oligodendrocyte Sgk1 expression to activity-dependent fluctuations in corticosterone hormone secretion, and raises the prospect that hypothalamic-pituitary-adrenal axis dysregulation or glucocorticoid pharmacotherapy may compromise the normal activity-dependent interactions between oligodendrocytes and neurons