scholarly journals Hypoxia upregulates the gene expression of mitochondrial aconitase in prostate carcinoma cells

2013 ◽  
Vol 51 (1) ◽  
pp. 131-141 ◽  
Author(s):  
Ke-Hung Tsui ◽  
Li-Chuan Chung ◽  
Shyi-Wu Wang ◽  
Tsui-Hsia Feng ◽  
Phei-Lang Chang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Carcinoma ◽  
Fatty Acid Synthase ◽  
Molecular Mechanisms ◽  
Transient Gene Expression ◽  
Carcinoma Cells ◽  
Human Prostate ◽  
Translation Initiation Site ◽  
Transcriptional Level ◽  
Mitochondrial Aconitase

Hypoxia induces metabolic alteration in cancer cells by stabilizing hypoxia-inducible factor 1α (HIF-1α (HIF1A)), which regulates the bioenergetic genes of glycolysis and lipid metabolic pathways. However, the target genes of hypoxia-induced metabolic alterations in the prostate remain uncertain. Mitochondrial aconitase (mACON) (ACONM) is an enzyme that is central to carbohydrate and energy metabolism and is responsible for the interconversion of citrate to isocitrate as part of the citric acid cycle in the human prostate. We evaluated the effects of the molecular mechanisms of hypoxia on mACON gene expression in PC-3 and LNCaP human prostate carcinoma cells. Immunoblotting assays revealed that hypoxia modulated mACON and lactate dehydrogenase A (LDHA) protein expression, while these effects were attenuated when HIF-1α was knocked down. Hypoxia induced fatty acid synthase (FASN) in PC-3 cells while hypoxia blocked FASN gene expression in LNCaP cells after 24-h incubation. Results of real-time RT-qPCR, immunoblotting, and transient gene expression assays revealed that hypoxia treatment or co-transfection with HIF-1α expression vector enhanced gene expression of mACON, implying that hypoxia modulated mACON at the transcriptional level. Hypoxia-induced mACON promoter activity is dependent on the DNA fragment located at −1013 to −842 upstream of the translation initiation site. l-mimosine, an iron chelator, stabilized HIF-1α but downregulated mACON gene expression, suggesting that iron chelation blocked the hypoxia-induced mACON gene expression. These results suggest that hypoxia dysregulates the expressions of LDHA, FASN, and mACON genes, and the hypoxia-induced mACON gene expression is via the HIF-1α-dependent and iron-dependent pathways in prostate carcinoma cells.

p53 downregulates the gene expression of mitochondrial aconitase in human prostate carcinoma cells

The Prostate ◽  
2010 ◽  
Vol 71 (1) ◽  
pp. 62-70 ◽  
Author(s):  
Ke-Hung Tsui ◽  
Tsui-Hsia Feng ◽  
Yu-Fen Lin ◽  
Phei-Lang Chang ◽  
Horng-Heng Juang
Keyword(s):  
Gene Expression ◽  
Prostate Carcinoma ◽  
Carcinoma Cells ◽  
Human Prostate ◽  
Mitochondrial Aconitase ◽  
Human Prostate Carcinoma

scholarly journals Testosterone modulates mitochondrial aconitase in the full-length human androgen receptor-transfected PC-3 prostatic carcinoma cells

2004 ◽  
Vol 33 (1) ◽  
pp. 121-132 ◽  
Author(s):  
HH Juang ◽  
ML Hsieh ◽  
KH Tsui
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
Androgen Receptor ◽  
Enzymatic Activity ◽  
Prostatic Carcinoma ◽  
Transient Gene Expression ◽  
Carcinoma Cells ◽  
Full Length ◽  
Mitochondrial Aconitase ◽  
Human Androgen Receptor

In vitro studies indicated that dihydrotestosterone (DHT) stimulates the enzymatic activity of the mitochondrial aconitase (mACON) in androgen-sensitive prostatic carcinoma cells, LNCaP. Cell proliferation assay determined that DHT doubles the optimal proliferation response of LNCaP cells. The androgen-insensitive human prostatic carcinoma cells, PC-3, were overexpressed in the human androgen receptor to assess the involvement of the native androgen receptor in the regulation by DHT of mACON gene expression. A stable-transfected clone that expresses the full-length androgen receptor was selected and termed PCAR9. The results revealed that DHT-treated PCAR9 cells paradoxically not only reduced the enzymatic activity of mACON but also blocked the biosynthesis of intracellular ATP attenuating cell proliferation. Transient gene expression assay indicated that DHT divergently regulates the promoter activity of the mACON gene in LNCaP and PCAR9 cells. This study suggested that DHT regulates mACON gene expression and the proliferation of cells in a receptor-dependent model through modulation by unidentified non-receptor factors.

Gene expression changes in human prostate carcinoma cells exposed to genotoxic and nongenotoxic aryl hydrocarbon receptor ligands

2011 ◽  
Vol 206 (2) ◽  
pp. 178-188 ◽  
Author(s):  
Eva Hrubá ◽  
Jan Vondráček ◽  
Helena Líbalová ◽  
Jan Topinka ◽  
Vítězslav Bryja ◽  
...  
Keyword(s):  
Gene Expression ◽  
Aryl Hydrocarbon Receptor ◽  
Prostate Carcinoma ◽  
Carcinoma Cells ◽  
Human Prostate ◽  
Receptor Ligands ◽  
Aryl Hydrocarbon ◽  
Human Prostate Carcinoma

l-Mimosine blocks cell proliferation via upregulation of B-cell translocation gene 2 and N-myc downstream regulated gene 1 in prostate carcinoma cells

2012 ◽  
Vol 302 (4) ◽  
pp. C676-C685 ◽  
Author(s):  
Li-Chuan Chung ◽  
Ke-Hung Tsui ◽  
Tsui-Hsia Feng ◽  
Shiow-Ling Lee ◽  
Phei-Lang Chang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Protein Expression ◽  
B Cell ◽  
Prostate Carcinoma ◽  
Molecular Mechanisms ◽  
Carcinoma Cells ◽  
Transcriptional Level ◽  
Lncap Cells ◽  
Protein Levels

l-Mimosine, an iron chelator and a prolyl 4-hydroxylase inhibitor, blocks many cancer cells at the late G1 phase. B-cell translocation gene 2 ( Btg2) regulates the G1/S transition phases of the cell cycle. N- myc downstream regulated gene 1 ( Ndrg1) is a differentiation-inducing gene upregulated by hypoxia. We evaluated the molecular mechanisms of l-mimosine on cell cycle modulation in PC-3 and LNCaP prostate carcinoma cells. The effect of l-mimosine on cell proliferation of prostate carcinoma cells was determined by the [3H]thymidine incorporation and flow cytometry assays. l-Mimosine arrested the cell cycle at the G1 phase in PC-3 cells and at the S phase in LNCaP cells, thus attenuating cell proliferation. Immunoblot assays indicated that hypoxia and l-mimosine stabilized hypoxia-inducible factor-1α (HIF-1α) and induced Btg2 and Ndrg1 protein expression, but downregulated protein levels of cyclin A in both PC-3 and LNCaP cells. l-Mimosine treatment decreased cyclin D1 protein in PC-3 cells, but not in LNCaP cells. Dimethyloxalylglycine, a pan-prolyl hydroxylase inhibitor, also induced Btg2 and Ndrg1 protein expression in LNCaP cells. The transient gene expression assay revealed that l-mimosine treatment or cotransfection with HIF-1α expression vector enhanced the promoter activities of Btg2 and Ndrg1 genes. Knockdown of HIF-1α attenuated the increasing protein levels of both Btg2 and Ndrg1 by hypoxia or l-mimosine in LNCaP cells. Our results indicated that hypoxia and l-mimosine modulated Btg2 and Ndrg1 at the transcriptional level, which is dependent on HIF-1α. l-Mimosine enhanced expression of Btg2 and Ndrg1, which attenuated cell proliferation of the PC-3 and LNCaP prostate carcinoma cells.

scholarly journals Thioredoxin-interacting protein: an oxidative stress-related gene is upregulated by glucose in human prostate carcinoma cells

2008 ◽  
Vol 42 (3) ◽  
pp. 205-214 ◽  
Author(s):  
See-Tong Pang ◽  
Wen-Chi Hsieh ◽  
Cheng-Keng Chuang ◽  
Chun-Hsiang Chao ◽  
Wen-Hui Weng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Glucose Metabolism ◽  
Prostate Carcinoma ◽  
Promoter Activity ◽  
Carcinoma Cells ◽  
Human Prostate ◽  
Response Element ◽  
Interacting Protein ◽  
Thioredoxin Interacting Protein ◽  
Human Prostate Carcinoma

Thioredoxin-interacting protein (TXNIP), also known as vitamin-D3 upregulated protein 1, interacts with reduced thioredoxin. This protein modulates the cellular redox state and plays a role in stress-induced cellular apoptosis. This study examined TXNIP gene expression in prostate cancer cells. In vitro studies by immunoblot assay have shown that elevated glucose levels (1–15 mM) upregulate TXNIP gene expression two- to fourfold in human prostate carcinoma cells (LNCaP) and hepatocellular carcinoma cells (HepG2). Transient gene expression assays reveal that the promoter activity of the TXNIP gene is upregulated by glucose, 3-O-methylglucose, and maltose, but not by mannitol. These results suggest that glucose and 3-O-methylglucose induce TXNIP expression through both glucose metabolism-dependent and -independent pathways. Cotransfection of a plasmid expression carbohydrate response element-binding protein (ChREBP) with a TXNIP reporter vector into LNCaP cells dramatically enhances reporter activity in a low glucose (1 mM) condition. The effects of glucose are apparently mediated in a region located −341 to −324 bp upstream of the translational starting point of the TXNIP gene as indicated by 5′-deletion and site-directed mutagenesis reporter assays. Mutation of the putative carbohydrate response element (ChoRE) from CACGAGGGCAGCACGAG to TTTGAGGGCAGCACGAG abolishes glucose upregulation of TXNIP promoter activity. The present study demonstrates that TXNIP is transcription induced in both LNCaP and HepG2 cells in an increased glucose metabolism-dependent or -independent response, and a putative glucose regulatory system including ChREBP and ChoRE is needed for glucose-induced TXNIP gene in human prostate carcinoma cells.

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