Differential Regulation of Vascular Endothelial Growth Factor Expression by Peroxisome Proliferator-activated Receptors in Bladder Cancer Cells

Fauconnet, Sylvie; Lascombe, Isabelle; Chabannes, É.; Adessi, G. L.; Desvergne, Béatrice; Wahli, Walter; Bittard, Hugues

doi:10.1074/jbc.m200172200

Cited by 107 publications

(75 citation statements)

References 56 publications

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“…In a previous study, we demonstrated that all PPAR are not only expressed but also functional in RT4 and T24 cells. 33 In the present work, contrary to previous studies in which A-FABP was not detected in T24 cells, we detected by western blotting analysis a very low quantity of A-FABP. As expected, A-FABP was expressed to a higher extent in RT4 cells than in T24 cells.…”

Section: Discussioncontrasting

confidence: 55%

A‐FABP, a candidate progression marker of human transitional cell carcinoma of the bladder, is differentially regulated by PPAR in urothelial cancer cells

Boiteux

Lascombe

Roche

et al. 2009

Intl Journal of Cancer

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Superficial pT1 bladder tumors are characterized by a high risk of recurrence and progression in grade and stage. Few studies provided evidence that loss of adipocyte-fatty acid binding protein (A-FABP) expression was associated with bladder cancer progression. A-FABP is a lipid binding protein playing a role in intracellular lipid transport and metabolism, as well as in signal transduction. We reported from bladder tumors that decrease of A-FABP transcript level significantly correlated to tumor stage and to histologic grade (p < 0.05). Namely, in poor prognosis high grade pT1 tumors there was a loss of A-FABP expression compared to good prognosis tumors suggesting that re-expression of A-FABP could be a therapeutic approach in early stage bladder cancer to prevent disease progression. We demonstrated for the first time that this marker is upregulated by Peroxisome Proliferator-Activated Receptor (PPAR) a, b and c in T24 cells (derived from an undifferentiated grade III carcinoma) and only by PPARb in RT4 cells (derived from a well differentiated grade I papillary tumor). This effect occurred through a PPAR-dependent transcriptional mechanism without modifying mRNA stability and interestingly required de novo protein synthesis. Data as a whole suggest a prognostic significance of A-FABP in bladder cancer outcome and the potential utility of overexpression of this protein by PPAR agonists open up new perspectives in the treatment of bladder cancer.

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Section: Discussioncontrasting

confidence: 55%

A‐FABP, a candidate progression marker of human transitional cell carcinoma of the bladder, is differentially regulated by PPAR in urothelial cancer cells

Boiteux

Lascombe

Roche

et al. 2009

Intl Journal of Cancer

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“…On the contrary, we did not reveal the 3.7 kb transcript and we detected for the first time to our knowledge in bladder cancer samples a shorter transcript of 1.7 kb in length. These three transcripts of 5.5, 4.5 and 1.7 kb had been already observed in a previous work performed in RT4 and T24 bladder cancer cell lines (31). This 1.7 kb transcript could be another VEGF-A isoform.…”

Section: Discussionmentioning

confidence: 88%

Expression analysis of VEGF-A and VEGF-B: Relationship with clinicopathological parameters in bladder cancer

Fauconnet¹

2009

Oncol Rep

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Abstract. The present investigation was conducted first to determine whether correlation exists between VEGF-A and -B mRNA levels and clinicopathological parameters and to assess their prognostic value in bladder cancer, then to clarify the expression level and biological significance of VEGF-A isoforms. Total RNA was isolated from 37 specimens of bladder cancer. Northern blot analysis revealed that VEGF-B mRNA was not expressed either in normal urothelium or in bladder cancer and detected three VEGF-A transcripts of 5.2, 4.5 and 1.7 kb in length, respectively. The VEGF-A transcript levels were greater in cancer tissues than in normal urothelium. They were significantly higher in pT2-T4 than in pTa and pT1 urothelial tumors and thus, were correlated to the pathologic stage. Contrary to the 4.5 kb transcript, elevated expression of the 5.2 and 1.7 kb transcripts was correlated with the histologic grade and the presence of carcinoma in situ. Patients with higher VEGF-A mRNA levels had a significantly shorter survival without progression compared to those with lower levels. Three VEGF-A splice variants were detected by Southern blotting namely, VEGF121, 165 and 189. The expression intensity of each isoform was evaluated by quantitative real-time RT-PCR in 20 new fresh frozen recent tumors. VEGF121 and VEGF165 were expressed at the similar level. On the contrary, they were significantly more expressed than VEGF189 (p<0.05). The three isoforms were higher expressed in pT2 bladder cancers than in pTa tumors (p<0.05). There was only a significant correlation between the increased expression level of VEGF121 and 165 and the histological grade of the lesion (p<0.05). To conclude, VEGF-A mRNA level is a potential prognostic indicator of progression in bladder cancer as well as the expression level of the different VEGF-A splice variants.

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“…Disruption of this gene was found to decrease tumorigenicity in colon cancer cells (27). Furthermore, PPARD regulates VEGF expression in bladder cancer cell lines (28). The 45 genes in the derived optimal prognosis signature were also found among the 200 best markers; however, the cross-validation approach also identified other interesting markers like BIRC5 (survivin), an apoptosis inhibitor that is up-regulated in the tumors that show later progression.…”

Section: Imaging Diagnosis Prognosismentioning

confidence: 96%

A Molecular Signature in Superficial Bladder Carcinoma Predicts Clinical Outcome

Dyrskjøt¹,

Zieger²,

Kruhøffer³

et al. 2005

Clinical Cancer Research

133

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Purpose: Cancer of the urinary bladder is a common malignant disease in the western countries. The majority of patients presents with superficial tumors with a high recurrence frequency, a minor fraction of these patients experience disease progression to a muscle invasive stage. No clinical useful molecular markers exist to identify patients showing later disease progression. The purpose of this study was to identify markers of disease progression using fullgenome expression analysis. Experimental Design: We did a full-genome expression analysis (59,619 genes and expressed sequence tags) of superficial bladder tumors from 29 bladder cancer patients (13 without later disease progression and 16 with later disease progression) using high-density oligonucleotide microarrays.We used supervised learning for identification of the optimal genes for predicting disease progression. The identified genes were validated on an independent test set (74 superficial tumor samples) using in house-fabricated 60-mer oligonucleotide microarrays. Results: We identified a 45-gene signature of disease progression. By monitoring this progression signature in an independent test set, we found a significant correlation between our classifications and the clinical outcome (P < 0.03). The genes identified as differentially expressed were involved in regulating apoptosis, cell differentiation, and cell cycle and hence may represent potential therapeutic targets. Conclusions: Our results indicate that it may be possible to identify patients with a high risk of disease progression at an early stage using a molecular signature present already in the superficial tumors. In this way, better treatment and follow-up regimens could be assigned to patients suffering from superficial bladder cancer.

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Differential Regulation of Vascular Endothelial Growth Factor Expression by Peroxisome Proliferator-activated Receptors in Bladder Cancer Cells

Cited by 107 publications

References 56 publications

A‐FABP, a candidate progression marker of human transitional cell carcinoma of the bladder, is differentially regulated by PPAR in urothelial cancer cells

A‐FABP, a candidate progression marker of human transitional cell carcinoma of the bladder, is differentially regulated by PPAR in urothelial cancer cells

Expression analysis of VEGF-A and VEGF-B: Relationship with clinicopathological parameters in bladder cancer

A Molecular Signature in Superficial Bladder Carcinoma Predicts Clinical Outcome

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