Transcription factor NRF2 is an important modifier of cellular responses to oxidative stress. Although its cytoprotective effects are firmly established, recent evidence suggesting important roles in cancer pathobiology has yet to be mechanistically developed. In the current study, we investigated the role of NRF2 in colon tumor angiogenesis. Stable RNAi-mediated knockdown of NRF2 in human colo...

Hypoxia is known to favor tumor survival and progression. Numerous studies have shown that hypoxiainducible factor 1a (HIF-1a), an oxygen-sensitive transcription factor, is overexpressed in various types of human cancers and upregulates a battery of hypoxia-responsive genes for the growth and survival of cancer cells. Although tumor progression involves the acquisition of genetic and/or epigene...

Hypoxia is an important regulator of vascular endothelial growth factor (VEGF) expression, and VEGF is associated with poor prognosis in bladder cancer. To investigate further the mechanisms of VEGF regulation, we examined VEGF expression by mRNA and protein analysis in four human bladder cancer cell lines, showing a progression from well to poorly differentiated phenotypes under varying condit...

Mammalian metallothionein (MT) genes are transcriptionally activated by the essential metal zinc as well as by environmental stresses, including toxic metal overload and redox fluctuations. In addition to playing a key role in zinc homeostasis, MT proteins can protect against metaland oxidant-induced cellular damage, and may participate in other fundamental physiologic and pathologic processes ...

Acute promyelocytic leukemia (APL) is epitomized by the chromosomal translocation t(15;17) and the resulting oncogenic fusion protein PML-RARa. Although acting primarily as a transcriptional repressor, PML-RARa can also exert functions of transcriptional co-activation. Here, we find that PML-RARa stimulates transcription driven by HIF factors, which are critical regulators of adaptive responses...

INTRODUCTION In contrast to estradiol action, little is known about androgen signaling in placental development. The purpose of this study was to evaluate the impact of diminished androgen action on hypoxia inducible factor 1a (HIF-1a) and vascular endothelial growth factor A (VEGFA) protein expression as well as their mRNAs in the structures of fetal and maternal parts of porcine placenta duri...

The rate of transcription of several genes encoding proteins involved in O2 and energy homeostasis is controlled by hypoxia-inducible factor-1 (HIF-1), a heterodimeric DNA binding complex composed of a and b subunits. HIF-1 is considered the primary trans-acting factor for the erythropoietin (EPO) and vascular endothelial growth factor (VEGF) genes. Since EPO gene expression is inhibited by the...

Vascular endothelial growth factor (VEGF)-dependent angiogenesis plays a crucial role in corpus luteum formation and its functional maintenance in mammalian ovaries. We recently reported that activation of hypoxia-inducible factor (HIF)-1α signaling contributes to the regulation of VEGF expression in luteal cells (LCs) in response to human chorionic gonadotropin (HCG). We examined whether HIF p...