Abstract:
:Normal cells produce energy either through OXPHOS in the presence of oxygen or glycolysis in its absence. Cancer cells produce energy preferably through glycolysis even in the presence of oxygen, thereby, acquiring survival and proliferative advantages. Oncogenes and tumour suppressors control these metabolic pathways by regulating the expression of their target genes involved in these processes. During hypoxia, HIF-1 favours high glycolytic flux by upregulating glycolytic enzymes. Conversely, p53 inhibits glycolysis and increases OXPHOS expression through TIGAR and SCO2 gene expression, respectively. We hypothesise that the p300/CBP-associated factor (PCAF) as a common co-factor shared between p53 and HIF-1 plays an important role in the regulation of energy production by modulating SCO2 and TIGAR gene expression mediated by these two transcription factors. The possible involvement of HIF-1 in the regulation of SCO2 and TIGAR gene expression was investigated in cells with different p53 status in normoxia- and hypoxia-mimicking conditions. Putative hypoxia response elements (HREs) were identified in the regulatory region of SCO2 and TIGAR gene promoters. Chromatin immunoprecipitation experiments suggested that HIF-1 was recruited to the putative HREs present in the SCO2 and TIGAR promoters in a cell type-dependent manner. Transcriptional assays endorsed the notion that PCAF may be involved in the determination of the SCO2 and TIGAR cellular levels, thereby, regulating cellular energy metabolism, a view supported by assays measuring lactic acid production and oxygen consumption in cells ectopically expressing PCAF. The present study identified HIF-1 as a potential regulator of SCO2 and TIGAR gene expression. Furthermore, evidence to suggest that PCAF is involved in the regulation of cellular energy production pathways in hypoxia-mimicking conditions is presented. This effect of PCAF is exerted by orchestrating differential recruitment of HIF-1α and p53 to the promoter of TIGAR and/or SCO2 genes, thereby, tailoring physiological needs and environmental conditions to SCO2 and TIGAR gene expression.
journal_name
Int J Oncoljournal_title
International journal of oncologyauthors
Rajendran R,Garva R,Ashour H,Leung T,Stratford I,Krstic-Demonacos M,Demonacos Cdoi
10.3892/ijo.2013.1907subject
Has Abstractpub_date
2013-06-01 00:00:00pages
1961-72issue
6eissn
1019-6439issn
1791-2423journal_volume
42pub_type
杂志文章abstract::The mutation of isocitrate dehydrogenase (IDH)1 (R132H) and IDH2 (R172K) and the induction of hypoxia in various solid tumors results in alterations in metabolic profiles, including the production of the d‑ or l‑forms of 2‑hydroxyglutarate (2HG) from α‑ketoglutarate in aerobic metabolism in the tricarboxylic acid (TCA...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2018.4649
更新日期:2019-02-01 00:00:00
abstract::The effects of pretreatment with the multidrug resistance (MDR) modulators verapamil (VPM), tamoxifen (TMX), cyclosporin A (CsA), and SDZ PSC833 (PSC) on drug sensitivity of the P-glycoprotein (Pgp) expressing human ileocecal carcinoma cell line HCT-8 is described. Following pretreatment of 2, 16 and 48 h with the ind...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.12.5.1137
更新日期:1998-05-01 00:00:00
abstract::Regulatory T cells (CD4+CD25+FoxP3+, Treg) have been shown to play a major role in suppression of the immune response to malignant gliomas. In this study, we investigated the kinetics of Treg infiltration in metastatic brain tumor models, including melanoma, breast and colon cancers. Our data indicate that both CD4+ a...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo_00000282
更新日期:2009-06-01 00:00:00
abstract::Prostate cancer is the most commonly diagnosed cancer and the second leading cause of cancer related deaths in men in the United States. Ciprofloxacin is a relatively non-toxic antibiotic that can be easily administered orally with large volume of distribution and good tissue penetration. Studies from others and our l...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2002-07-01 00:00:00
abstract::Serum CASA, CEA, CYFRA 21-1, NSE, MSA, TPA, and TPS were determined in patients with lung cancer (LC), benign lung disease (BL), and healthy control (HC) donors. Using predefined cutpoints, the cytokeratin-related markers TPA, TPS, and CYFRA showed the highest sensitivity in non-small cell lung cancer (TPA 69%, TPS 63...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.4.5.1129
更新日期:1994-05-01 00:00:00
abstract::Lamins are the major components of the nuclear lamina and play important roles in many cellular processes. The role of lamins in cancer development and progression is still unclear but it is known that reduced expression of lamin B1 has been observed in colon cancer. Thus, the aim of the present study was to elucidate...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2017.4182
更新日期:2018-01-01 00:00:00
abstract::The p16INK4 gene, encoding a cyclin-dependent kinase inhibitor, is frequently methylated in colorectal cancer, and a side-specific methylation frequency was suggested. To clarify the frequency of real loss of tumor suppressor function dependent on anatomical localization, we investigated 43 primary colorectal carcinom...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2003-10-01 00:00:00
abstract::Claudin 6 (CLDN6), a member of tight junction protein claudin (CLDN) family, inhibits proliferation and induces apoptosis of MCF-7 breast cancer cells. However, these molecular mechanisms of CLDN6-induced apoptosis remain largely elusive. We previously found that restoration of human CLDN6 gene expression was correlat...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2016.3469
更新日期:2016-06-01 00:00:00
abstract::Currently, it is not entirely clear whether hypoxia-inducible factor-1α (HIF-1α) is involved in the regulation of COX-2 expression and epithelial-to-mesenchymal transition (EMT), and whether these events affect the prognosis of hepatocellular carcinoma (HCC) patients treated with transcatheter arterial chemoembolizati...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2016.3421
更新日期:2016-05-01 00:00:00
abstract::Human malignant neuroblastoma is characterized by poor differentiation and uncontrolled proliferation of immature neuroblasts. Retinoids such as all-trans-retinoic acid (ATRA), 13-cis-retinoic acid (13-CRA), and N-(4-hydroxyphenyl) retinamide (4-HPR) at low doses are capable of inducing differentiation, while flavonoi...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo_00000201
更新日期:2009-03-01 00:00:00
abstract::The MUC1 heterodimeric protein is aberrantly overexpressed in diverse human carcinomas and contributes to the malignant phenotype. The MUC1-C transmembrane subunit contains a CQC motif in the cytoplasmic domain that has been implicated in the formation of dimers and in its oncogenic function. The present study demonst...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2011.1308
更新日期:2012-05-01 00:00:00
abstract::The MyD118/Gadd45/CR6 gene family (also termed Gadd45beta/alpha/gamma) has been identified as genes which are rapidly induced by genotoxic agents, during terminal differentiation, as well as by apoptotic cytokines. In recent years, evidence has emerged that the proteins encoded by these genes play pivotal roles in neg...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2001-04-01 00:00:00
abstract::Vascular endothelial growth factor (VEGF) has four isoforms (VEGF121, VEGF165, VEGF189, VEGF206). We examined the expression patterns of VEGF isoforms in non-small cell lung cancer (NSCLC) by RT-PCR. The cell-associated isoform VEGF189 was more frequently expressed in NSCLC (90.5%) than in extraneoplastic lung tissue ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.12.3.541
更新日期:1998-03-01 00:00:00
abstract::Histone deacetylase inhibitors (HDACIs) are involved in cell growth, apoptosis and differentiation. This study aimed to investigate the effects of HDACI scriptaid on histone modification, demethylation, cell growth, cell cycle and apoptosis in the RKO colorectal cancer cell line and screening for scriptaid-induced gen...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2008-10-01 00:00:00
abstract::Due to the central role in predicting response to herceptin and possibly also other anticancer drugs, accurate and reproducible detection of the HER2 status is important. Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) are the most commonly used methods for HER2 analysis. It is a disadvantage ...
journal_title:International journal of oncology
pub_type: 临床试验,杂志文章
doi:
更新日期:2004-12-01 00:00:00
abstract::Interleukin-2 (IL-2) which has no cross-resistance with chemotherapy, has given responses in tumors resistant to chemotherapy, and shown to be more effective when tumor burden is low. 13-cis retinoic acid (RA) has immunomodulatory properties, potentially synergistic with IL-2. The objective of this pilot phase II stud...
journal_title:International journal of oncology
pub_type: 临床试验,杂志文章
doi:
更新日期:2002-06-01 00:00:00
abstract::Although CD138 expression is a hallmark of plasma cells and myeloma cells, reduced CD138 expression is occasionally found. However, the mechanisms underlying CD138 downregulation in myeloma cells remain unclear. Previous reports suggest that the bone marrow microenvironment may contribute to CD138 downregulation. Amon...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2013.2134
更新日期:2013-12-01 00:00:00
abstract::Clinicopathological assessment of the functional relationship between the HER2 oncogene and tumor-associated fatty acid synthase (FASN) is largely precluded because immunohistochemical and/or mRNA studies should be performed in biopsies from breast cancer patients. We here sought to determine whether serum FASN (sFASN...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo_00000455
更新日期:2009-12-01 00:00:00
abstract::Sonic hedgehog (SHH), Indian hedgehog (IHH) and Desert hedgehog (DHH) are Hedgehog family ligands, which play key roles in embryogenesis and carcinogenesis, especially in pancreatic cancer and gastric cancer. Drosophila Costal-2 (Cos2) is a Hedgehog signaling regulator, interacting with Smoothened (Smo), Cubitus inter...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2004-12-01 00:00:00
abstract::Cytokines of the TGF beta family are thought to be involved in cellular growth control and are therefore likely candidates to regulate homeostasis of the prostate. We have analyzed immunohistochemically the expression of TGF-beta 3 in normal prostate (NP), benign prostate hyperplasia (BPH) and prostate cancer (PCa). I...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.11.6.1185
更新日期:1997-12-01 00:00:00
abstract::The platinum complex trans-[PtCl2¿E-HN=C(OMe)Me¿2] was compared to cisplatin for cytotoxicity towards tumour cells, and for cellular pharmacological properties in A2780 and cisplatin-resistant A2780/Cp8 ovarian cancer cells. Trans-[PtCl2¿E-HN=C(OMe)Me¿2] was comparably cytotoxic to cisplatin (mean IC50 after 72 h expo...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.15.5.1039
更新日期:1999-11-01 00:00:00
abstract::Although active targeting of anticancer drugs using magnetically responsive carriers is a very attractive treatment approach for solid tumors, successful results are limited. In particular, the therapeutic utility of intravenously administered magnetically responsive carriers has to date not been clearly established. ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.17.2.309
更新日期:2000-08-01 00:00:00
abstract::Serum ferritin is elevated in many cancers. Using the subtraction-enhanced display technique, we isolated several cDNA clones including ferritin-H which is overexpressed in rat hepatocellular carcinoma (HCC) induced by diethylnitrosamine. We investigated hepatic messenger RNA (mRNA) levels of ferritin-H in patients wi...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.11.1.187
更新日期:1997-07-01 00:00:00
abstract::Primary cilia are microtubule-based organelles that regulate smoothened-dependent activation of the GLI transcription factors in canonical hedgehog signaling. In many cancers, primary cilia are markedly decreased or absent. The lack of primary cilia may inhibit or alter canonical hedgehog signaling and, thereby, inter...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2015.3006
更新日期:2015-07-01 00:00:00
abstract::Specific RE protein species modulated by autocrine TGF alpha are unknown. HCT116 cells transfected with TGF alpha antisense expression vector were compared with control HCT116 NEO for mitogenesis and modulation of high MW (130, 120 kD) and low MW (116, 110, 105 kD) RE species. Nutrients alone (N) induced maximal mitog...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.8.6.1025
更新日期:1996-06-01 00:00:00
abstract::The effects of a thymic peptide preparation (TP) on the immunocytotoxicity and cytokine secretion of peripheral blood lymphocytes and monocytes from patients with colorectal tumors, breast tumors and melanoma were studied in vitro. On average, breast tumor and melanoma patients showed significantly lower natural kille...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.10.3.481
更新日期:1997-03-01 00:00:00
abstract::Prostate cancer (CaP), the most common malignancy in American men, presents its greatest challenge to clinicians when the cancer progresses to the hormone-refractory state. In the present investigation, we studied the combined effects of interferon (IFN) and onconase, each of which has reported antitumor activity, on ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2002-05-01 00:00:00
abstract::The development of targeted molecular therapies has greatly benefited patients with lung adenocarcinomas. In contrast, these treatments have had little benefit in the management of lung squamous cell carcinoma (lung SCC). Therefore, new treatment options based on current genomic approaches are needed for lung SCC. Abe...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2016.3690
更新日期:2016-11-01 00:00:00
abstract::Methylenetetrahydrofolate reductase (MTHFR) catalyzes the synthesis of 5-methyltetrahydrofolate, which is involved in the methylation of homocysteine to methionine. Genetic polymorphisms that decrease MTHFR activity result in an altered cancer risk depending on folic acid intake. In this study we examined the C677T an...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2004-11-01 00:00:00
abstract::Intracellular antigens are presented to CD8+ T cells through major histocompatibility complex (MHC) class I molecule. For stable MHC class I expression, several molecules as well as the MHC molecule itself have to express simultaneously and function well. To determine a gene associated with MHC class I surface express...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.16.6.1159
更新日期:2000-06-01 00:00:00