Reciprocal relationship between expression of hypoxia inducible factor 1α (HIF-1α) and the pro-apoptotic protein Bid in ex vivo colorectal cancer

Seenath, Marlon; Roberts, D. F.; Cawthorne, Christopher; Saunders, Mark; Armstrong, G. R.; O’Dwyer, Sarah T; Stratford, Ian J.; Renehan, Andrew G

doi:10.1038/sj.bjc.6604474

Cited by 12 publications

(10 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Specifically, HIF-1 can downregulate pro-apoptotic Bid, the reversal of which is associated with enhanced chemotherapy response (Brown et al, 2006). The reciprocal relationship between HIF-1a and Bid expression is maintained in clinical samples of CRC, supporting its potential importance (Seenath et al, 2008). With current interest in the development of HIF-targeting agents as novel cancer therapies, these data would support their exploitation in combination with standard chemotherapy to enhance the treatment response in CRC.…”

Section: Discussionmentioning

confidence: 86%

Contribution of HIF-1 and drug penetrance to oxaliplatin resistance in hypoxic colorectal cancer cells

et al. 2009

Self Cite

View full text Add to dashboard Cite

BACKGROUND: Hypoxia is as an indicator of poor treatment outcome. Consistently, hypoxic HCT116 colorectal cancer cells are resistant to oxaliplatin, although the mechanistic basis is unclear. This study sought to investigate the relative contribution of HIF-1 (hypoxia-inducible factor-1)-mediated gene expression and drug penetrance to oxaliplatin resistance using three-dimensional spheroids. METHODS: Hypoxia-inducible factor-1a function was suppressed by the stable expression of a dominant-negative form in HCT116 cells (DN). Cells were drug exposed as monolayer or multicellular spheroid cultures. Cells residing at differing oxygenation status were isolated from Hoechst 33342-treated spheroids using flow cytometry. Sub-populations were subjected to clonogenic survival assays and to Inductively-Coupled Plasma Mass Spectroscopy to determine oxaliplatin uptake. RESULTS: In spheroids, a sensitivity gradient (hypoxicoaerobic) was revealed by survival assays and this correlated with levels of platinum-bound DNA. The resistance of hypoxic sub-populations exceeded relative changes in adduct levels, implicating factors other than drug penetrance in cell response. Dominant-negative monolayer cells showed no resistance to oxaliplatin in hypoxia and spheroids; the relative resistance of hypoxic compared with aerobic sub-populations was reduced compared with those from controls. CONCLUSION: Overall, data show that drug penetration, DNA damage levels and HIF-1-dependent processes, all contribute to the resistance of hypoxic cells to oxaliplatin.

show abstract

Section: Discussionmentioning

confidence: 86%

Contribution of HIF-1 and drug penetrance to oxaliplatin resistance in hypoxic colorectal cancer cells

et al. 2009

Self Cite

View full text Add to dashboard Cite

show abstract

“…The relationship between IR and IGF-IR expression was determined in serial tumour sections from 17 patients with colonic adenocarcinomas immune-stained as described previously in our laboratory ( 34 ). Stained slides were scanned using a Mirax SCAN automated slide scanning system (Zeiss).…”

Section: Methodsmentioning

confidence: 99%

A framework for thein vitroevaluation of cancer-relevant molecular characteristics and mitogenic potency of insulin analogues

Baricevic¹,

Jones

Roberts³

et al. 2015

CARCIN

View full text Add to dashboard Cite

show abstract

“…Furthermore, in high HIF-1α nuclear-positive cell subpopulations of 39 human colorectal adenocarcinomas, there was a significant reduction in Bid expression. (30) Many previous studies by us have shown that ST13 gene expression levels are significantly decreased in primary colorectal cancers compared with adjacent mucosal tissues. (18,31) It raises the question of whether the low expression of ST13 is due to hypoxia in colorectal tumors.…”

Section: Discussionmentioning

confidence: 99%

Potent antitumor activity of double‐regulated oncolytic adenovirus‐mediated ST13 for colorectal cancer

Zhong

Yang

et al. 2009

Cancer Science

View full text Add to dashboard Cite

Following targeted gene virotherapy, the suppression of tumorigenicity 13 (ST13) gene was inserted into the doubleregulated oncolytic adenovirus SG500 to ensure more safety and potent antitumor activity against colorectal cancer in vitro and in vivo. We generated the ST13-expressing oncolytic adenovirus SG500-ST13, with which colorectal carcinoma cell lines SW620 and HCT116, and the lung fibroblast cell line WI38, were infected. Crystal violet staining was carried out to detect the cytopathic effect in cells, and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method was used to assay cell viability. The effect of apoptosis induced by SG500-ST13 was confirmed by Hoechst staining and the TdT-mediated dUTP-biotin nick-end labeling method. To further identify the antitumor effects of SG500-ST13 on HCT116 xenografts in Balb/c nude mice, the induction of cell death was assessed by hematoxylin-eosin staining. Immunohistochemical study was also carried out. (Cancer Sci 2009; 100: 678-683) C olorectal cancer ranks second in both morbidity and mortality in developed countries. Nearly 945 000 new colorectal cancer cases are diagnosed worldwide each year and its mortality rate is approximately 492 000.(1) Despite advanced progress in technologies for diagnosis and therapy, around 50% of newly diagnosed colorectal cancer patients will die of this disease due to metastases.(2) Surgical resection or surgery coupled with systemic chemotherapy of liver metastasis is the treatment currently available for these patients.(3) These findings underscore the need for improved therapeutic approaches to more efficaciously control this aggressive type of cancer and reduce its metastatic spread.Conditional replicative adenoviruses appear to be attractive anticancer agents that are currently being evaluated in clinical trials.(4,5) CRAd exerts intrinsic anticancer activity through its selective replication in and lysis of cancer cells. In addition, release of CRAd progeny by infected tumor cells provides a potential to amplify the oncolytic effect and its lateral spread through solid tumors.One strategy to ensure tumor targeting is to place the virual essential genes under the control of tumor-specific promoters. Because the hTERT promoter is expected to be active in the majority (~90%) of human cancer cells with upregulated telomerase expression, (6) the hTERT promoter is used to control the essential gene E1A for adenovirus replication in a series of CRAd.(7-9) Hypoxia occurs in virtually all solid tumors as they outgrow their blood supply. Hypoxia augments cellular levels of HIF, a transcription factor that regulates target genes through the binding of HRE. Activation of the HIF pathway enables cancer cells to survive and proliferate in a hypoxic environment and contributes to a more aggressive phenotype.(10,11) Therefore, the HIF-HRE system of gene regulation under hypoxia, or as a result of genetic alterations during cell transformation, is particularly attractive to specifically target solid tumors. Therefore, HRE ha...

show abstract

Reciprocal relationship between expression of hypoxia inducible factor 1α (HIF-1α) and the pro-apoptotic protein Bid in ex vivo colorectal cancer

Cited by 12 publications

References 17 publications

Contribution of HIF-1 and drug penetrance to oxaliplatin resistance in hypoxic colorectal cancer cells

Contribution of HIF-1 and drug penetrance to oxaliplatin resistance in hypoxic colorectal cancer cells

A framework for thein vitroevaluation of cancer-relevant molecular characteristics and mitogenic potency of insulin analogues

Potent antitumor activity of double‐regulated oncolytic adenovirus‐mediated ST13 for colorectal cancer

Contact Info

Product

Resources

About