Tumor hypoxia often directly correlates with aggressive phenotype, metastasis progression, and resistance to chemotherapy. Two transcription factors [hypoxia-inducible factor-1A (HIF-1A) and HIF-2A] are dramatically induced in hypoxic areas and regulate the expression of genes necessary for tumor adaptation to the conditions of low oxygen; however, the relative contribution of these factors is controversial. We used RNA interference-mediated inactivation of HIF-1A or HIF-2A followed by microarray analysis to identify genes specifically regulated by either HIF-1 or HIF-2 in hypoxia. We found that, in the MCF7 cell line, the vast majority of hypoxiaresponsive genes (>80%) were dependent on the presence of HIF-1A. However, a small group of genes were preferentially regulated by HIF-2A. Promoter analysis for this group of genes revealed that all of them have putative binding sites for ETS family transcription factors, and 10 of 11 HIF-2A-dependent genes had at least one potential hypoxia-responsive element (HRE) in proximity to an ETS transcription factor binding site. Knockdown of ELK-1, the most often represented member of ETS family, significantly reduced hypoxic induction of the HIF-2A-dependent genes. Physical and functional interaction between ELK-1 and HIF-2A were supported by coimmunoprecipitation of these two proteins, luciferase reporter assay using CITED2 promoter, and binding of ELK-1 protein to the promoters of CITED2 and WISP2 genes in proximity to a HRE. These data suggest that the choice of the target genes by HIF-1 or HIF-2 depends on availability and cooperation of HIFs with other factors recognizing their cognate elements in the promoters. (Cancer Res 2006; 66(11): 5641-7)

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Students' LE perceptions are closely associated with their well-being, and fostering peer community may hold promise for enhancing quality of life and protecting against burnout. Across these three settings, LE and empathy were not closely related, suggesting that any influence of learning environment on empathy would be modest.

"Etiquette-based medicine" was infrequently practiced by this sample of hospitalist physicians. Improving performance of etiquette-based medicine may improve patient satisfaction.