Searching for Hif1-α interacting proteins in renal cell carcinoma

Villaamil, Vanessa Medina; Gallego, Guadalupe Aparicio; Caínzos, I. Santamarina; Valladares‐Ayerbes, Manuel; Aparicio, Luís M. Antón

doi:10.1007/s12094-012-0857-4

Cited by 14 publications

(14 citation statements)

References 34 publications

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“…The protein products of these genes participate in both protecting the cell against hypoxia and activating angiogenesis. Among the genes in question there are carbonic anhydrase 9, vascular endothelial growth factors and their receptors, glucose transporter 1 and others [12][13][14][15][16].…”

Section: Discussionmentioning

confidence: 99%

Selected immunohistochemical features of conventional renal cell carcinomas coexpressing P53 and MDM2

Hejnold¹,

Dyduch²,

Białas³

et al. 2014

pjp

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Renal clear cell carcinoma (CCRCC) is an aggressive tumor for which new prognostic factors are needed. It has been suggested that CCRCCs co-expressing P53 and MDM2 could represent a special subgroup; therefore the aim of this study was to explore their immunohistochemical features. The material studied consisted of 470 cases of CCRCC. Immunohistochemistry for MDM2, P53, Ki-67, VEGF-A, VEGF-C, VEGF-D, GLUT1, CA9, and CK 7 was performed on tissue microarrays and assessed semi-quantitatively. On average, 6.6% or 5.3% of cases were P53+/ MDM2+, depending on the P53 antibody used. The mean percentage of Ki-67 positive cells was 0.6% and p53-positive MDM2-positive cases showed significantly higher expression of Ki-67. The other immunohistochemical parameters studied did not differ between p53-positive MDM2-positive cases and the rest of the subtypes studied. Expression of almost all immunohistochemical markers differed with respect to pT stage; only for CA9 was the difference not significant. Furthermore, almost all immunohistochemical markers studied differed with respect to differences in grade; only for GLUT1 was the difference not significant. Our results suggest that with the exception of Ki-67, there are no significant associations between analyzed markers and the double P53+/MDM2+ phenotype.

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Section: Discussionmentioning

confidence: 99%

Selected immunohistochemical features of conventional renal cell carcinomas coexpressing P53 and MDM2

Hejnold¹,

Dyduch²,

Białas³

et al. 2014

pjp

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“…Schultz et al [61] showed that HIF1α levels were significantly higher in primary and metastatic ccRCCs compared with benign tissues (P<0.0001), and that tumor size and HIF1α expression were independent predictors of both reduced disease free survival and tumor progression in primary ccRCC. In another recent report, the highest level of HIF1α expression in ccRCCs was associated with the worst prognoses [60]. Studies have also examined both HIF1α and HIF2α in the same tissue samples.…”

Section: Reviewmentioning

confidence: 99%

“…Of note, HIF1α expression correlates significantly with the “clear” histological subtype of renal cell carcinoma (p<0.01) [60], possibly because HIF1α (and not HIF2α) increases the expression of lipin1, a phosphatidate phosphatase that catalyzes the last step in triglyceride biosynthesis [64]. Triglycerides form lipid droplets, the major neutral lipid stores in cells, and these lipid droplets cause the “clear” phenotype in human ccRCC.…”

Section: Reviewmentioning

confidence: 99%

The role of HIF1α in renal cell carcinoma tumorigenesis

Gudas

Minton

et al. 2014

J Mol Med

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The transcription factor HIF1α is implicated in the development of clear cell renal cell carcinoma (ccRCC). Although HIF1α was initially believed to be essential for ccRCC development, recent studies hypothesize an oncogenic role for HIF2α in ccRCC, but a tumor suppressor role for HIF1α [1], leading to uncertainty as to the precise roles of the different HIF transcription factors in this disease. Using evidence available from studies with human ccRCC cell lines, mouse xenografts, murine models of ccRCC, and human ccRCC specimens, we evaluate the roles of HIF1α and HIF2α in the pathogenesis of ccRCC. We present a convergence of clinical and mechanistic data supporting an important role for HIF1α in promoting tumorigenesis in a clinically important and large subset of ccRCC. This indicates that current understanding of the exact roles of HIF1α and HIF2α is incomplete and that further research is required to determine the diverse roles of HIF1α and HIF2α in ccRCC.

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“…The functional form of the pVHL in association with elongin C, elongin B, cullin2 (Cul2), neural precursor cell expressed developmentally down-regulated 8 (Nedd8) and ring-box 1 (RBX1) forms a multi-protein complex called E3 ubiquitin ligase (or VEC) able in turn to bind the hydroxylated form of the subunit α of the transcription hypoxia-inducible factor (HIF) [4,5,6,7]. In normoxic conditions the formation of this complex leads to the degradation of HIF, while in case of hypoxia the stabilized form (non-hydroxylated) HIF is able to induce the transcription of genes that leads to the secretion of pro-angiogenic factors (such as vascular endothelial growth factor (VEGF) and platelet derived growth factor-β (PDGF-β)), Glucose transporter 1 (GLUT-1) and erythropoietin [4,5,6,7,8] (Figure 1). Over the last few years the ever-deeper knowledge on the molecular biology of metastatic RCC has led to the development of numerous molecular targeting agents (such as sunitinib, sorafenib, pazopanib, axitinib, tivozanib, and dovitinib) [9].…”

Section: Introductionmentioning

confidence: 99%

Possible Prognostic and Therapeutic Significance of c-Kit Expression, Mast Cell Count and Microvessel Density in Renal Cell Carcinoma

Marech

Gadaleta

Ranieri

2014

IJMS

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Renal cell carcinoma (RCC) is the most frequent renal tumor and its incidence is increasing worldwide. Tumor angiogenesis is known to play a crucial role in the etiopathogenesis of RCC and over the last few years an even deeper knowledge of its contribution in metastatic RCC development has led to the development of numerous molecular targeting agents (such as sunitinib, sorafenib, pazopanib, axitinib, tivozanib, and dovitinib). The above agents are principally directed against vascular endothelial growth factor receptor (VEGFR) members and also against c-Kit receptor (c-KitR). The role of c-kitR inhibition on clear cell RCC (ccRCC), the main RCC subtype, is less well established. Whether c-kitR activation through its ligand, stem cell factor (SCF) contributes significantly to the effects of tyrosine kinase inhibitors (TKIs) treatment remains to be established. It is important to underscore that the c-KitR is expressed on mast cells (MCs) and cancer cells. After an examination of the c-KitR/SCF pathway, we review here the principal studies that have evaluated c-Kit expression in RCC. Moreover, we summarize some investigations that have observed the distribution of MCs in primary renal cancer and in adjacent normal tissue with appropriate histological immunohistochemical techniques. We also focus on few studies that have evaluated the correlation between RCC proliferation, MC count and microvessel density (MVD), as hallmarks of tumor angiogenesis. Thus, the aim of this review of the literature is to clarify if c-KitR expression, MC count and MVD could have prognostic significance and the possible predictive therapeutic implications in RCC.

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Searching for Hif1-α interacting proteins in renal cell carcinoma

Cited by 14 publications

References 34 publications

Selected immunohistochemical features of conventional renal cell carcinomas coexpressing P53 and MDM2

Selected immunohistochemical features of conventional renal cell carcinomas coexpressing P53 and MDM2

The role of HIF1α in renal cell carcinoma tumorigenesis

Possible Prognostic and Therapeutic Significance of c-Kit Expression, Mast Cell Count and Microvessel Density in Renal Cell Carcinoma

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