Correlation study showing no concordance between EPAS-1/HIF-2α mRNA and protein expression in transitional cellcancer of the bladder

Ji, P G; Xuan, Jim W.; Onita, Toru; Sakai, Hideki; Kanetake, Hiroshi; Gabril, Manal; Sun, Yunming; Moussa, Madeleine; Chin, Joseph L.

doi:10.1016/s0090-4295(02)02405-6

Cited by 11 publications

(14 citation statements)

References 15 publications

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“…We also observed that tumors with lower expression recurred earlier. On the contrary, HIF-2 ␣ stromal tumor cells expression was correlated with more advance tumor stage according to previous studies [29,30] . These data could suggest differences in the contribution of tumor HIF-2 ␣ and stromal cells HIF-2 ␣ expression in the biological behavior of bladder cancer.…”

Section: Discussionmentioning

confidence: 64%

“…HIF-2 ␣ , another important transcriptional activator, is known to be upregulated in cancer. Previous studies [29,30] concerning the EPAS-1/HIF-2 ␣ protein expression in bladder biopsy samples, using the mouse monoclonal anti-EPAS-1 antibody, revealed that its overexpression was found mainly in the stromal tissues around the cancer cells, in the tumor-associated macrophages and in the perinecrotic regions. There was no expression of EPAS-1/HIF-2 ␣ in cancer cells in all the cases.…”

Section: Discussionmentioning

confidence: 98%

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Hypoxia-Inducible Factors HIF-1α and HIF-2α Expression in Bladder Cancer and Their Associations with Other Angiogenesis-Related Proteins

Ioachim

Michael²,

Salmas³

et al. 2006

Urol Int

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Hypoxia-inducible factors (HIF-1α and HIF-2α) are closely related protein complexes that activate transcription of target genes in response to hypoxia. The immunohistochemical expression of these two proteins was investigated in 144 bladder cancer tissue samples and correlated with standard clinicopathological features, in order to elucidate their prognostic significance. We also evaluated their possible associations with other angiogenesis related markers such as microvessel density (MVD), vascular endothelial growth factor, thymidine phosphorylase, tenascin, fibronectin, p53 and bcl-2 to further clarify their implication in tumor stroma vascularization. Nuclear HIF-1α expression in tumor cells was detected in 57.1% of the cases. A trend of correlation of this expression with poorly differentiated tumors was observed. In addition, HIF-1α expression was positively correlated with stromal cells thymidine phosphorylase expression. Tumors that were progressed in muscle-infiltrating disease showed a higher HIF-1α expression. A higher HIF-1α expression was also observed in tumors with an in situ component. In tumor cells, low HIF-2α expression was observed in 6.3%, moderate in 31.9% and high in 61.8% of the cases. A trend of correlation of this expression with MVD was observed. In addition, HIF-2α expression was positively correlated with thymidine phosphorylase and fibronectin expression. A lower HIF-2α expression was detected in tumors that recurred earlier in univariate methods of analysis. HIF-2α was expressed in tumor stroma associated cells in 53.5% of specimens and was correlated with advance tumor stage, thymidine phosphorylase and tenascin expression. There was no statistically significant difference in the expression of both HIF-1α and HIF-2α between primary and recurrent tumors. In multivariate analysis including T stage, T grade, multifocality and T size, both HIF-1α and HIF-2α expression were not considered dependent in the prediction of recurrence or progression. In conclusion, the results of the present study indicate that HIF-1α and HIF-2α expression may help to predict recurrence or progression to muscle invasive disease but not as independent prognostic factors. In addition, the expression of HIF-1α and HIF-2α, appear to play a role in bladder cancer, vascularization possibly and in cooperation with other angiogenic factors.

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Section: Discussionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 98%

Hypoxia-Inducible Factors HIF-1α and HIF-2α Expression in Bladder Cancer and Their Associations with Other Angiogenesis-Related Proteins

Ioachim

Michael²,

Salmas³

et al. 2006

Urol Int

View full text Add to dashboard Cite

show abstract

“…First, we studied the whole kidneys from diabetic animals, whereas Clarkson et al studied mesangial cells in vitro. Second, changes in mRNA and protein do not always correlate (35)(36)(37)(38). Third, differential protein expression can result from posttranslational modifications that are not detectable by genomic analysis.…”

Section: Discussionmentioning

confidence: 99%

Alterations in the Renal Elastin-Elastase System in Type 1 Diabetic Nephropathy Identified by Proteomic Analysis

Thongboonkerd¹,

Barati²,

McLeish

et al. 2004

Journal of the American Society of Nephrology

100

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Abstract. Diabetes now accounts for Ͼ40% of patients with ESRD. Despite significant progress in understanding diabetic nephropathy, the cellular mechanisms that lead to diabetesinduced renal damage are incompletely defined. For defining changes in protein expression that accompany diabetic nephropathy, the renal proteome of 120-d-old OVE26 transgenic mice with hypoinsulinemia, hyperglycemia, hyperlipidemia, and proteinuria were compared with those of background FVB nondiabetic mice (n ϭ 5). Proteins derived from whole-kidney lysate were separated by two-dimensional PAGE and identified by matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) mass spectrometry. Forty-one proteins from 300 visualized protein spots were differentially expressed in diabetic kidneys. Among these altered proteins, expression of monocyte/neutrophil elastase inhibitor was increased, whereas elastase IIIB was decreased, leading to the hypothesis that elastin expression would be increased in diabetic kidneys. Renal immunohistochemistry for elastin of 325-d-old FVB and OVE26 mice demonstrated marked accumulation of elastin in the macula densa, collecting ducts, and pelvicalyceal epithelia of diabetic kidneys. Elastin immunohistochemistry of human renal biopsies from patients with type 1 diabetes (n ϭ 3) showed increased elastin expression in renal tubular cells and the interstitium but not glomeruli. These results suggest that coordinated changes in elastase inhibitor and elastase expression result in increased tubulointerstitial deposition of elastin in diabetic nephropathy. The identification of these coordinated changes in protein expression in diabetic nephropathy indicates the potential value of proteomic analysis in defining pathophysiology.Diabetes now accounts for Ͼ40% of patients with ESRD, and the number of renal failure patients with diabetes is expected to increase in the coming years (1). Renal pathologic changes that lead to decreased renal function are observed in all intrarenal structures, including glomeruli, tubulointerstitium, and blood vessels (2, 3). These morphologic changes, coupled with elevated intraglomerular pressure and hormonal dysregulation, lead to glomerulosclerosis, interstitial fibrosis, and ultimately renal failure (4, 5). Despite recent progress in understanding diabetic nephropathy, the cellular mechanisms that lead to diabetes-induced renal damage are incompletely defined.Recently, Clarkson et al. (6) demonstrated that at least 200 genes were differentially expressed in mesangial cells after exposure to high-glucose media. These findings indicate the complexity of the development of diabetic nephropathy. However, proteins, not genes, govern cellular functions. The study of changes in renal protein expression is necessary to understand better the complex pathogenic mechanisms of diabetic nephropathy. Conventional protein studies-Western blotting and other immunologic methods-are limited to a relatively small number of proteins that can be studied in each experiment and to previously ide...

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“…[72][73][74][75] As a prognostic marker high HIF-2α relates to advanced stage and/or poor patient outcome in several tumor forms. Among these are non-small cell lung cancer, 76 breast cancer, 77,78 bladder cancer, 72,79 colorectal cancer, 80 and neuroblastoma. 69 While many cell line and mouse model studies show an undisputed role of HIF-2α in VHL disease and clear-cell RCC 81,82 there are, however, few studies…”

Section: Hif-2α In Cancermentioning

confidence: 99%

“…69,76,78,93,94 There seem to be tumor type-specific differences regarding the question whether HIF-2α expression correlates positively or negatively to increased microvessel counts, 79,80 presumably reflecting HIF-stabilizing induction mechanisms other than hypoxia. Of note, stromal cell thymidine phosphorylase is involved in regulating tumor angiogenesis, 95 stressing the importance of tumor-stroma interactions in malignant progression.…”

confidence: 99%

Hypoxia Inducible Factor-2α in Cancer

Löfstedt¹,

Fredlund²,

Mengelbier³

et al. 2007

Cell Cycle

172

142

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Correlation study showing no concordance between EPAS-1/HIF-2α mRNA and protein expression in transitional cellcancer of the bladder

Cited by 11 publications

References 15 publications

Hypoxia-Inducible Factors HIF-1α and HIF-2α Expression in Bladder Cancer and Their Associations with Other Angiogenesis-Related Proteins

Hypoxia-Inducible Factors HIF-1α and HIF-2α Expression in Bladder Cancer and Their Associations with Other Angiogenesis-Related Proteins

Alterations in the Renal Elastin-Elastase System in Type 1 Diabetic Nephropathy Identified by Proteomic Analysis

Hypoxia Inducible Factor-2α in Cancer

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