Faculty Opinions recommendation of Regulation of the histone demethylase JMJD1A by hypoxia-inducible factor 1 alpha enhances hypoxic gene expression and tumor growth.

2009 ◽  
Author(s):  
Steven A Rosenzweig
Keyword(s):  
Gene Expression ◽  
Tumor Growth ◽  
Hypoxia Inducible Factor ◽  
Histone Demethylase ◽  
Hypoxia Inducible Factor 1

scholarly journals Hypoxia-inducible factor-1 modulates gene expression in solid tumors and influences both angiogenesis and tumor growth

1997 ◽  
Vol 94 (15) ◽  
pp. 8104-8109 ◽  
Author(s):  
P. H. Maxwell ◽  
G. U. Dachs ◽  
J. M. Gleadle ◽  
L. G. Nicholls ◽  
A. L. Harris ◽  
...  
Keyword(s):  
Gene Expression ◽  
Tumor Growth ◽  
Solid Tumors ◽  
Hypoxia Inducible Factor ◽  
Hypoxia Inducible Factor 1

scholarly journals Regulation of the Histone Demethylase JMJD1A by Hypoxia-Inducible Factor 1α Enhances Hypoxic Gene Expression and Tumor Growth

2009 ◽  
Vol 30 (1) ◽  
pp. 344-353 ◽  
Author(s):  
Adam J. Krieg ◽  
Erinn B. Rankin ◽  
Denise Chan ◽  
Olga Razorenova ◽  
Sully Fernandez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Tumor Growth ◽  
Histone Methylation ◽  
Hypoxia Inducible Factor ◽  
Histone Demethylase ◽  
Carcinoma Cell Lines ◽  
Signal Amplifier ◽  
Reduce Tumor Growth ◽  
Inducible Genes

ABSTRACT The hypoxia-inducible transcription factors (HIFs) directly and indirectly mediate cellular adaptation to reduced oxygen tensions. Recent studies have shown that the histone demethylase genes JMJD1A, JMJD2B, and JARID1B are HIF targets, suggesting that HIFs indirectly influence gene expression at the level of histone methylation under hypoxia. In this study, we identify a subset of hypoxia-inducible genes that are dependent on JMJD1A in both renal cell and colon carcinoma cell lines. JMJD1A regulates the expression of adrenomedullin (ADM) and growth and differentiation factor 15 (GDF15) under hypoxia by decreasing promoter histone methylation. In addition, we demonstrate that loss of JMJD1A is sufficient to reduce tumor growth in vivo, demonstrating that histone demethylation plays a significant role in modulating growth within the tumor microenvironment. Thus, hypoxic regulation of JMJD1A acts as a signal amplifier to facilitate hypoxic gene expression, ultimately enhancing tumor growth.

scholarly journals Accelerated tumor growth under intermittent hypoxia is associated with hypoxia-inducible factor-1-dependent adaptive responses to hypoxia

Oncotarget ◽  
2017 ◽  
Vol 8 (37) ◽  
pp. 61592-61603 ◽  
Author(s):  
Dae Wui Yoon ◽  
Daeho So ◽  
Sra Min ◽  
Jiyoung Kim ◽  
Mingyu Lee ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Intermittent Hypoxia ◽  
Hypoxia Inducible Factor ◽  
Adaptive Responses ◽  
Hypoxia Inducible Factor 1

scholarly journals Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1.

1996 ◽  
Vol 16 (9) ◽  
pp. 4604-4613 ◽  
Author(s):  
J A Forsythe ◽  
B H Jiang ◽  
N V Iyer ◽  
F Agani ◽  
S W Leung ◽  
...  
Keyword(s):  
Gene Expression ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Reporter Gene ◽  
Hypoxia Inducible Factor ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
Vascular Endothelial ◽  
Hypoxia Inducible Factor 1 ◽  
Endothelial Growth Factor

Expression of vascular endothelial growth factor (VEGF) is induced in cells exposed to hypoxia or ischemia. Neovascularization stimulated by VEGF occurs in several important clinical contexts, including myocardial ischemia, retinal disease, and tumor growth. Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric basic helix-loop-helix protein that activates transcription of the human erythropoietin gene in hypoxic cells. Here we demonstrate the involvement of HIF-1 in the activation of VEGF transcription. VEGF 5'-flanking sequences mediated transcriptional activation of reporter gene expression in hypoxic Hep3B cells. A 47-bp sequence located 985 to 939 bp 5' to the VEGF transcription initiation site mediated hypoxia-inducible reporter gene expression directed by a simian virus 40 promoter element that was otherwise minimally responsive to hypoxia. When reporters containing VEGF sequences, in the context of the native VEGF or heterologous simian virus 40 promoter, were cotransfected with expression vectors encoding HIF-1alpha and HIF-1beta (ARNT [aryl hydrocarbon receptor nuclear translocator]), reporter gene transcription was much greater in both hypoxic and nonhypoxic cells than in cells transfected with the reporter alone. A HIF-1 binding site was demonstrated in the 47-bp hypoxia response element, and a 3-bp substitution eliminated the ability of the element to bind HIF-1 and to activate transcription in response to hypoxia and/or recombinant HIF-1. Cotransfection of cells with an expression vector encoding a dominant negative form of HIF-1alpha inhibited the activation of reporter transcription in hypoxic cells in a dose-dependent manner. VEGF mRNA was not induced by hypoxia in mutant cells that do not express the HIF-1beta (ARNT) subunit. These findings implicate HIF-1 in the activation of VEGF transcription in hypoxic cells.

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