PubMed · 14228909
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E L BIERMAN. 1964. RADIOACTIVE FAT ABSORPTION TESTS.. https://pubmed.ncbi.nlm.nih.gov/14228909/
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The ETS transcription factor Fifth Ewing Variant (FEV) mRNA, a homologue of the rodent Pet-1 gene that is exclusively expressed in serotonin-containing neurons and is a critical determinant of serotonin neuronal differentiation and development, was examined in human postmortem brain tissue using in situ hybridization histochemistry. Studies revealed that FEV mRNA is robustly and exclusively expressed in the major serotonin-containing cell groups of the dorsal and median raphe nuclei located in the midbrain and pons of the human brainstem. The localization of transcription factor, FEV, mRNA in serotonin-containing neurons of the human brain raises questions regarding the functional significance of this transcription factor in regulating serotonin-related genes and its potential role in psychiatric illness.
In the late nineteenth century, microscopists developed a quaint method for examining the fine structure of biological specimens: paraffin embedding and staining with hematoxylin and eosin. This ancient technology is here to stay for the foreseeable future, because it can and does reveal the truth about biological processes. However, the role of pathology is developing with ever greater world wide interaction between pathologists, and better communication and agreeing of international standards. Furthermore, recent techniques including immunohistochemistry, electron microscopy and image analysis complement the traditional tried and tested tools. There is also in toxicologic pathology a willingness to use pathology methods and skills in new contexts, drug discovery in particular. But even in these days of genetic modification, proteomics and high throughput screening, pathologists continue to rely on dyes extracted from a Central American logwood used in Mexico before the Spanish invasion in 1520.
Hypoxia stimulates a number of pathways critical to cancer cell survival, including the activation of vascular endothelial growth factor (VEGF) transcription. In normal fibroblasts, hypoxia-induced activation of the protein tyrosine kinase, Src, is required for VEGF expression. We show here in both pancreatic and prostate carcinoma cell lines cobalt chloride (used to mimic hypoxia) -induced VEGF expression requires Src activation and leads to increased steady-state levels of HIF-1alpha and increased phosphorylation of signal and transducer of transcription 3 (STAT3). STAT3 and hypoxia-inducible factor (HIF)-1alpha bind simultaneously to the VEGF promoter, where they form a molecular complex with the transcription coactivators CBP/p300 and Ref-1/APE. Expression of activated Src from an inducible promoter is sufficient to increase VEGF expression and form these STAT3/HIF-1alpha-containing promoter complexes. Inhibition of DNA binding by expression of either STAT3 or HIF-1alpha dominant negative mutants significantly reduces VEGF expression. These data suggest that the binding of both STAT3 and HIF-1alpha to the VEGF promoter is required for maximum transcription of VEGF mRNA following hypoxia.