Abstract:
BACKGROUND:Aldo-keto reductase (AKR) 1C family member 3 (AKR1C3), one of four identified human AKR1C enzymes, catalyzes steroid, prostaglandin, and xenobiotic metabolism. In the prostate, AKR1C3 is up-regulated in localized and advanced prostate adenocarcinoma, and is associated with prostate cancer (PCa) aggressiveness. Here we propose a novel pathological function of AKR1C3 in tumor angiogenesis and its potential role in promoting PCa progression. METHODS:To recapitulate elevated AKR1C3 expression in cancerous prostate, the human PCa PC-3 cell line was stably transfected with an AKR1C3 expression construct to establish PC3-AKR1C3 transfectants. Microarray and bioinformatics analysis were performed to identify AKR1C3-mediated pathways of activation and their potential biological consequences in PC-3 cells. Western blot analysis, reverse transcription-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and an in vitro Matrigel angiogenesis assays were applied to validate the pro-angiogenic activity of PC3-AKR1C3 transfectants identified by bioinformatics analysis. RESULTS:Microarray and bioinformatics analysis suggested that overexpression of AKR1C3 in PC-3 cells modulates estrogen and androgen metabolism, activates insulin-like growth factor (IGF)-1 and Akt signaling pathways, as well as promotes tumor angiogenesis and aggressiveness. Levels of IGF-1 receptor (IGF-1R) and Akt activation as well as vascular endothelial growth factor (VEGF) expression and secretion were significantly elevated in PC3-AKR1C3 transfectants in comparison to PC3-mock transfectants. PC3-AKR1C3 transfectants also promoted endothelial cell (EC) tube formation on Matrigel as compared to the AKR1C3-negative parental PC-3 cells and PC3-mock transfectants. Pre-treatment of PC3-AKR1C3 transfectants with a selective IGF-1R kinase inhibitor (AG1024) or a non-selective phosphoinositide 3-kinases (PI3K) inhibitor (LY294002) abolished ability of the cells to promote EC tube formation. CONCLUSIONS:Bioinformatics analysis followed by functional genomics demonstrated that AKR1C3 overexpression promotes angiogenesis and aggressiveness of PC-3 cells. These results also suggest that AKR1C3-mediated tumor angiogenesis is regulated by estrogen and androgen metabolism with subsequent IGF-1R and Akt activation followed by VEGF expression in PCa cells.
journal_name
BMC Cancerjournal_title
BMC cancerauthors
Dozmorov MG,Azzarello JT,Wren JD,Fung KM,Yang Q,Davis JS,Hurst RE,Culkin DJ,Penning TM,Lin HKdoi
10.1186/1471-2407-10-672subject
Has Abstractpub_date
2010-12-06 00:00:00pages
672issn
1471-2407pii
1471-2407-10-672journal_volume
10pub_type
杂志文章相关文献
BMC CANCER文献大全abstract:BACKGROUND:PRDM5 is an epigenetic regulator that has been recognized as an important tumour suppressor gene. Silencing of PRDM5 by promoter hypermethylation has been demonstrated in several cancer types and PRDM5 loss results in upregulation of the Wnt pathway and increased cellular proliferation. PRDM5 has not been ex...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-015-1011-9
更新日期:2015-01-23 00:00:00
abstract:BACKGROUND:Many studies have reported the prognostic significance of the bone scan index (BSI) for metastatic castration-resistant prostate cancer (mCRPC); however, these reports are controversial. This study investigated the BSI in mCRPC and its relationship with prognosis. METHODS:The PubMed, Cochrane, and Embase da...
journal_title:BMC cancer
pub_type: 杂志文章,meta分析
doi:10.1186/s12885-020-06739-y
更新日期:2020-03-20 00:00:00
abstract:BACKGROUND:To evaluate the effect of Recurrence Score® results (RS; Oncotype DX® multigene assay ODX) on treatment recommendations by Swiss multidisciplinary tumor boards (TB). METHODS:SAKK 26/10 is a multicenter, prospective cohort study of early breast cancer patients: Eligibility: R0-resection, ≥10% ER+ malignant c...
journal_title:BMC cancer
pub_type: 杂志文章,多中心研究
doi:10.1186/s12885-017-3261-1
更新日期:2017-04-13 00:00:00
abstract:BACKGROUND:The cytochrome P450 (CYP) enzymes 2C19, 2D6, and 3A5 are responsible for converting the selective estrogen receptor modulator (SERM), tamoxifen to its active metabolites 4-hydroxy-tamoxifen (4OHtam) and 4-hydroxy-N-demethyltamoxifen (4OHNDtam, endoxifen). Inter-individual variations of the activity of these ...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/1471-2407-10-313
更新日期:2010-06-21 00:00:00
abstract:BACKGROUND:The mixture of volatile organic compounds in the headspace gas of urine may be able to distinguish lung cancer patients from relevant control populations. METHODS:Subjects with biopsy confirmed untreated lung cancer, and others at risk for developing lung cancer, provided a urine sample. A colorimetric sens...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-015-1996-0
更新日期:2015-12-23 00:00:00
abstract:BACKGROUND:This study aimed to identify potential predictive factors for the survival of advanced non small-cell lung cancer (NSCLC) patients undergoing first-line platinum-based chemotherapy. METHODS:A total of 270 advanced NSCLC patients who underwent first-line platinum-based chemotherapy from June, 2011 to June, 2...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-019-5490-y
更新日期:2019-03-29 00:00:00
abstract:BACKGROUND:Tobacco smoking is associated with a unique mutational signature in the human cancer genome. It is unclear whether tobacco smoking-altered DNA methylations and gene expressions affect smoking-related mutational signature. METHODS:We systematically analyzed the smoking-related DNA methylation sites reported ...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-020-07368-1
更新日期:2020-09-14 00:00:00
abstract:BACKGROUND:Several studies show that the regulatory impact of microRNAs (miRNAs) is an essential contribution to the pathogenesis of colorectal cancer (CRC). The expression levels of diverse miRNAs are associated with specific clinical diagnoses and prognoses of CRC. However, this association reveals very little action...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-015-1437-0
更新日期:2015-06-18 00:00:00
abstract:BACKGROUND:For the expanding population of bladder cancer survivors in Korea, the development of subsequent cancers is a significant concern. Here, we provide the second primary cancer incidence rates and types in Korean patients with bladder cancer. METHODS:Using population-based data from the Korea Central Cancer Re...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-018-4530-3
更新日期:2018-05-31 00:00:00
abstract:BACKGROUND:The immune system plays an important role in the multifactorial biologic system during the development of neoplasias. However, the involvement of the inflammatory response in the promotion/control of malignant cells is still controversial, and the cell subsets and the mechanisms involved are poorly investiga...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/1471-2407-10-256
更新日期:2010-06-04 00:00:00
abstract:BACKGROUND:Survival rates of lung cancer remains poor and the impact of comorbidities on the prognosis is discussed. The objective of this study was to assess if the Charlson Comorbidity Index (CCI) was associated with 8-year survival rates by histological type. METHODS:A cohort study was conducted using randomly sele...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-018-5000-7
更新日期:2018-11-12 00:00:00
abstract:BACKGROUND:Lymphangiogenesis has become a new research frontier in tumor metastasis since the discovery of reliable lymphatic markers that have allowed observation and isolation of lymphatic endothelium. Cyclooxygenase-2 (COX-2) has been reported to be involved in the critical steps in carcinogenesis. However, possible...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/1471-2407-8-4
更新日期:2008-01-13 00:00:00
abstract:BACKGROUND:It has been shown that peroxisome proliferator-activated receptors (PPAR) have physiological and pharmacological ligands. The objective is to assess the association between thiazolidinediones (TZDs) and the occurrence of gastric cancer. METHODS:We conducted a population-based nested case-control study. Data...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/1471-2407-13-420
更新日期:2013-09-17 00:00:00
abstract:BACKGROUND:Cyclooxygenases (COX) play a key role in prostaglandin metabolism and are important for tumor development and progression. The aim of this study was to analyze the prognostic impact of COX-2 expression in a cohort of lymph node-negative breast cancer patients not treated in the adjuvant setting. METHODS:COX...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/1471-2407-14-952
更新日期:2014-12-15 00:00:00
abstract:BACKGROUND:Identifying cellular signaling pathways that become corrupted in the presence of androgens that increase the metastatic potential of organ-confined tumor cells is critical to devising strategies capable of attenuating the metastatic progression of hormone-naïve, organ-confined tumors. In localized prostate c...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-015-1201-5
更新日期:2015-03-31 00:00:00
abstract:BACKGROUND:Advanced biliary tract carcinomas (BTCs) have poor prognosis and limited therapeutic options. Therefore, it is crucial to combine standard therapies with molecular targeting. In this study EGFR, HER2, and their molecular transducers were analysed in terms of mutations, amplifications and over-expression in a...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/1471-2407-10-631
更新日期:2010-11-18 00:00:00
abstract:BACKGROUND:The phenomenon that malignant cells can acquire stemness under specific stimuli, encompassed under the concept of cancer cell plasticity, has been well-described in epithelial malignancies. To our knowledge, cancer cell plasticity has not yet been described in hematopoietic cancers. To illustrate and study c...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-018-4300-2
更新日期:2018-04-02 00:00:00
abstract:BACKGROUND:To determine the safety and efficacy of transarterial chemoembolization (TACE) combined with radiofrequency ablation (hereafter, TACE-RFA) in treating Barcelona Clinic Liver Cancer (BCLC) Stage A or B (hereafter, BCLC A/B) hepatocellular carcinoma (HCC) patients, and to explore the range of tumor sizes suita...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-019-6237-5
更新日期:2019-10-22 00:00:00
abstract:BACKGROUND:To compare the survival outcomes and acute toxicities of concurrent chemoradiotherapy (CCRT), induction chemotherapy (IC) plus radiotherapy (RT), and IC plus CCRT in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) treated using intensity-modulated radiotherapy (IMRT). METHODS:Patients w...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-015-1768-x
更新日期:2015-10-27 00:00:00
abstract:BACKGROUND:Two functional single nucleotide polymorphisms (SNPs) in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, C677T and A1298C, lead to decreased enzyme activity and affect chemosensitivity of tumor cells. We investigated whether these MTHFR SNPs were associated with breast cancer survival in African-A...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/1471-2407-6-257
更新日期:2006-10-27 00:00:00
abstract:BACKGROUND:Antiangiogenic therapies are considered promising for the treatment of glioblastoma (GB). The non-collagenous C-terminal globular NC1 domain of type VIII collagen a1 chain, Vastatin, is an endogenous antiangiogenic polypeptide. Sustained enhanced expression of Vastatin was shown to inhibit tumour growth and ...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-017-3125-8
更新日期:2017-02-13 00:00:00
abstract:BACKGROUND:Well-designed clinical trials are of great importance in validating novel treatments and ensuring an evidence-based approach for sarcoma. This study aimed to provide a comprehensive landscape of the characteristics of metastatic or advanced sarcoma clinical trials using the substantial resource of the Clinci...
journal_title:BMC cancer
pub_type: 杂志文章,meta分析
doi:10.1186/s12885-018-5163-2
更新日期:2018-12-13 00:00:00
abstract:BACKGROUND:Although preoperative radiotherapy (RT) is widely used as the initial treatment for locally advanced rectal cancer (RC) in the neoadjuvant setting, factors determining clinical response have not been adequately defined. In order to find other factors possibly related with radiosensitivity, we evaluated the r...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/1471-2407-11-64
更新日期:2011-02-10 00:00:00
abstract:BACKGROUND:Pneumatosis cystoides intestinalis (PCI) is a rare self-limiting condition characterized by air-filled cysts within intestinal walls. Diagnosis should be prudent because it can mimic pneumoperitoneum leading to unnecessary treatment such as surgical exploration. Although various drugs including anti-neoplast...
journal_title:BMC cancer
pub_type: 杂志文章,评审
doi:10.1186/s12885-017-3744-0
更新日期:2017-11-09 00:00:00
abstract:BACKGROUND:The molecular chaperone, heat shock protein 90 (Hsp90) has been shown to be overexpressed in a number of cancers, including prostate cancer, making it an important target for drug discovery. Unfortunately, results with N-terminal inhibitors from initial clinical trials have been disappointing, as toxicity an...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/1471-2407-11-468
更新日期:2011-10-31 00:00:00
abstract:BACKGROUND:Lung cancer patients with an activating mutation in the EGFR (epidermal growth factor receptor) can develop resistance to erlotinib treatment, which is often mediated by the T790M resistance mutation in EGFR. The difficulties in obtaining biopsies at progression make it challenging to investigate the appeara...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-018-4108-0
更新日期:2018-02-15 00:00:00
abstract:BACKGROUND:This study aimed to evaluate the short- and long-term outcomes after laparoscopic resection for low rectal cancer (LRC) compared with mid/high rectal cancer (M/HRC). METHODS:Patients with rectal cancer undergoing laparoscopic resection with curative intent were retrospectively reviewed between 2009 and 2015...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-020-07255-9
更新日期:2020-08-14 00:00:00
abstract:BACKGROUND:H. pylori, whose infection increases tumor invasiveness and metastasis, is generally labelled as the strongest risk factor for the development of gastric cancer. It appears not to be a coincidence that there is also an overexpression of CXCR4 and an obvious involvement in gastric cancer metastasis. The aim o...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/1471-2407-10-419
更新日期:2010-08-11 00:00:00
abstract:BACKGROUND:The application of induction chemotherapy failed to provide a consistent benefit for local control in primary treatment of advanced head and neck (H&N) cancers. The aim of this study was to compare the results of concomitant application of radiochemotherapy for treating locally advanced head-and-neck carcino...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/1471-2407-6-30
更新日期:2006-02-01 00:00:00
abstract:BACKGROUND:To investigate whether MRI findings, including texture analysis, can differentiate KRAS mutation status in rectal cancer. METHODS:Totally, 158 patients with pathologically proved rectal cancers and preoperative pelvic MRI examinations were enrolled. Patients were stratified into two groups: KRAS wild-type g...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-019-6341-6
更新日期:2019-11-14 00:00:00