Quantitative comparison of mRNA level of corticotropin- releasing factor peptide family in normal kidney and corresponding clear cell renal cell carcinoma specimens.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 466-466
Author(s):  
Hossein Tezval ◽  
Axel S. Merseburger ◽  
Markus A. Kuczyk ◽  
Christoph von Klot ◽  
Juergen Serth
Keyword(s):  
Cell Carcinoma ◽  
Clear Cell ◽  
Mrna Level ◽  
Corticotropin Releasing Factor ◽  
Mrna Levels ◽  
Normal Kidney ◽  
Cell Renal Cell Carcinoma ◽  
Inhibition Of Proliferation ◽  
Peptide Family ◽  
Crf System

466 Background: Urocortin (Ucn), a 40 amino acid peptide, belongs to the corticotropin releasing factor (CRF) family and exerts its actions mainly in the periphery through activation of two CRF receptors (CRFRs), CRFR1 and CRFR2 and a binding protein (CRFBP/CRHBP). Both receptors are G-protein coupled and binding of Ucn leads to activation of cAMP-dependent protein kinases via elevation of cAMP levels. Ucn and Urocortin III (UcnIII) are involved in conditions such as regulation of local inflammation, angiogenesis, and inhibition of proliferation. Suppression of neovascularization and inhibition of tumor cell cycling by Urocortins is modulated through CRFRs. Activation of CRFRs by e.g. Ucn inhibits angiogenesis via reduction of vascular endothelial growth factor (VEGF) and suppresses the cell proliferation. Here we characterized the whole CRF family on mRNA levels quantitatively comparing the normal and clear cell carcinoma of the kidney (ccRCC). Methods: In this study we measured the mRNA level of Ucn, UcnIII, CRFR1, CRFR2 and CRHBP in 78 RCC samples and paired histologically normal appearing tissues using quantitative PCR. Statistical analyses were carried out using univariate logistic regression analysis. Results: We found tumour specific down regulation of mRNA expression of UcnIII, CRFR1, CRFR2 and CRHBP in samples of RCCs with clear cell histology compared to paired normal tissues (P<0.01 for all targets). Only Ucn did not show any expression difference between two groups (p=0.17). Conclusions: For the first time we showed the expression profile of the whole CRF peptide family in ccRCC compared to normal kidney on mRNA level. Our data underlines the malfunction of this actually strong protective and anticancer system in renal malignancy and shows the involvement of CRF system in carcinogenesis in kidney. More studies are necessary to find out the detailed roles of the CRF system in renal carcinoma.

scholarly journals IgG is involved in the migration and invasion of clear cell renal cell carcinoma

2015 ◽  
Vol 69 (6) ◽  
pp. 497-504 ◽  
Author(s):  
Zhengzuo Sheng ◽  
Yang Liu ◽  
Caipeng Qin ◽  
Zhenhua Liu ◽  
Yeqing Yuan ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Western Blot ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Renal Cell ◽  
Clear Cell ◽  
Migration And Invasion ◽  
Cancer Therapies ◽  
Normal Kidney ◽  
Cell Renal Cell Carcinoma

OBJECTIVE:To investigate if IgG can be expressed in clear cell renal cell carcinoma (cRCC) , and the expression of IgG is involved in the cancer progression. If IgG expression can serve as a potential target in cancer therapies and be used for judging the prognosis.MATERIALS AND METHODS:By immunohistochemistry, we detected IgG in cRCC tissues(75 cRCC tissues and75 adjacent normal kidney tissues). Immunofluorescence and Western blot was used to detect the IgG in cRCC cell lines (786-0, ACHN and CAKI-I). By RT-PCR, the functional transcript of IgG heavy chain was detected. Knockdown of IgG was to analyze the proliferation, migration and invasion ability by CCK8, Transwell and Matrigel and apoptosis in cRCC cell lines.RESULTS:By immunohistochemistry, we found strong staining of IgG in 66 cases of 75 cRCC tissues and 63 cases of 75 adjacent normal kidney tissues. Immunofluorescence and Western blot was found IgG in cRCC cell lines. Knock-down IgG in cRCC cell lines resulted in significant inhibition of cell proliferation, migration and invasion, and the induction of apoptosis of the 786-0 cells. The immunohistochemistry analysis showed that high IgG expression significantly correlated with the poor differentiation and advanced stage of cRCC.CONCLUSION:IgG was over expressed in cRCC and was involved in the proliferation, migration and invasion of cancer cells. IgG expression may serve as a potential target in cancer therapies and could be used for judging the prognosis.

scholarly journals New monoclonal antibodies against bilitranslocase as a diagnostic tool in determining the progress of clear cell renal cell carcinoma

2017 ◽  
Vol 86 (5-6) ◽  
Author(s):  
Alexandra Bogožalec Košir ◽  
Tjaša Lukan ◽  
Mateja Kukovec ◽  
Sendi Montanič ◽  
Vivijana Snoj ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Monoclonal Antibodies ◽  
Cell Carcinoma ◽  
Cell Line ◽  
Diagnostic Tool ◽  
Renal Cell ◽  
Clear Cell ◽  
Kidney Cells ◽  
Normal Kidney ◽  
Cell Renal Cell Carcinoma

Background: Monoclonal antibodies (mAbs) are an important tool in diagnostics and research, especially when we are dealing with a protein marker of unknown primary structure as in the case of bilitranslocase (BTL). BTL is also expressed on kidney cells, where it acts as an organic anion transporter. We have shown earlier that there are differences in bilitranslocase expression in normal kidney cells versus early grade kidney cancer.Methods: We developed monoclonal antibodies against extra- and intra-cellular domains of bilitranslocase protein model. To also gain a deeper insight in bilitranslocase expression in clinical samples, we assessed BTL expression in different grades of clear cell kidney cell carcinoma (ccRCC).Results: Both new monoclonal antibodies bind to a protein in UOK171 cells but not in the negative control. Binding of mAb is specifc. mAb produced by cell line 2A9/2E9 (peptide 298–310; intracellular domain) is more suitable for immunohistochemical analyses as it gives stronger intensity of binding than mAb produced by cell line 11C9/2G9 (peptide 235–246; extracellular domain). Antibody 2A9/2E9 stains bilitranslocase in proximal renal tubules of normal kidneys but not in the surrounding stroma. Staining decreases in grade I compared to normal kidney, gradually increases in grades II and III, and decreases again in grade IV of ccRCC tissue.Conclusions: Our results show that these antibodies can be used in different immunoassays. Furthermore, specificity and afnity of our mAbs allowed us to use them in the analysis of progressive grades of clear cell renal cell carcinoma in a limited number of patients. Tus, mAbs developed here can be used as a diagnostic tool that could help distinguish between early and late grades of clear cell renal cell carcinoma.

scholarly journals Hypoxia-inducible factor (HIF)-prolyl hydroxylase 3 (PHD3) maintains high HIF2A mRNA levels in clear cell renal cell carcinoma

2019 ◽  
Vol 294 (10) ◽  
pp. 3760-3771 ◽  
Author(s):  
Petra Miikkulainen ◽  
Heidi Högel ◽  
Fatemeh Seyednasrollah ◽  
Krista Rantanen ◽  
Laura L. Elo ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Hypoxia Inducible Factor ◽  
Prolyl Hydroxylase ◽  
Mrna Levels ◽  
Cell Renal Cell Carcinoma ◽  
Hif Prolyl Hydroxylase

scholarly journals Expression of AOX1 Predicts Prognosis of Clear Cell Renal Cell Carcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Luyang Xiong ◽  
Yuchen Feng ◽  
Wei Hu ◽  
Jiahong Tan ◽  
Shusheng Li ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Differentially Expressed Genes ◽  
Renal Cell ◽  
Clear Cell ◽  
Metabolic Reprogramming ◽  
Differentially Expressed ◽  
Normal Kidney ◽  
Cell Renal Cell Carcinoma ◽  
Cancer Management

Clear cell renal cell carcinoma (ccRCC) is the most prevalent kidney cancer worldwide, and appropriate cancer biomarkers facilitate early diagnosis, treatment, and prognosis prediction in cancer management. However, an accurate biomarker for ccRCC is lacking. This study identified 356 differentially expressed genes in ccRCC tissues compared with normal kidney tissues by integrative analysis of eight ccRCC datasets. Enrichment analysis of the differentially expressed genes unveiled improved adaptation to hypoxia and metabolic reprogramming of the tumor cells. Aldehyde oxidase 1 (AOX1) gene was identified as a biomarker for ccRCC among all the differentially expressed genes. ccRCC tissues expressed significantly lower AOX1 than normal kidney tissues, which was further validated by immunohistochemistry at the protein level and The Cancer Genome Atlas (TCGA) data mining at the mRNA level. Higher AOX1 expression predicted better overall survival in ccRCC patients. Furthermore, AOX1 DNA copy number deletion and hypermethylation were negatively correlated with AOX1 expression, which might be the potential mechanism for its dysregulation in ccRCC. Finally, we illustrated that the effect of AOX1 as a tumor suppressor gene is not restricted to ccRCC but universally exists in many other cancer types. Hence, AOX1 may act as a potential prognostic biomarker and therapeutic target for ccRCC.

Role of AMPK/mTOR-independent autophagy in clear cell renal cell carcinoma

2020 ◽  
Vol 68 (8) ◽  
pp. 1386-1393
Author(s):  
Milan Radovanovic ◽  
Sasenka Vidicevic ◽  
Jelena Tasic ◽  
Nina Tomonjic ◽  
Zeljka Stanojevic ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Tumor Stage ◽  
Autophagic Flux ◽  
Mrna Levels ◽  
Cell Renal Cell Carcinoma ◽  
Protein Levels

We examined the status and role of autophagy, a process of lysosomal recycling of cellular material, in clear cell renal cell carcinoma (ccRCC). Paired samples of tumor and adjacent non-malignant tissue were collected from 20 patients with ccRCC after radical nephrectomy. The mRNA levels of apoptosis (BAD, BAX, BCL2, BCLXL, BIM) and autophagy (ATG4, BECN1, GABARAP, p62, UVRAG) regulators were measured by RT-qPCR. The protein levels of autophagosome-associated LC3-II, autophagy receptor p62, apoptotic marker PARP, as well as phosphorylation of autophagy initiator Unc 51-like kinase 1 (ULK1), its activator AMP-activated protein kinase (AMPK) and 4EBP1, the substrate of ULK1 inhibitor mechanistic target of rapamycin (mTOR), were analyzed by immunoblotting. The mRNA levels of pro-apoptotic BAX, anti-apoptotic BCLXL and pro-autophagic ATG4, p62 and UVRAG were higher in ccRCC tumors. Autophagy induction was confirmed by an increase in phospho-ULK1 and degradation of the autophagic target p62, while apoptotic PARP cleavage was unaltered. AMPK phosphorylation was reduced and 4EBP1 phosphorylation was increased in ccRCC tissue. The expression of apoptosis regulators did not correlate with clinicopathological features of ccRCC. Conversely, high mRNA levels of ATG4, GABARAP and p62 were associated with lower tumor stage, as well as with smaller tumor size and better disease-specific 5-year survival (ATG4 and p62). Accordingly, low p62 protein levels, corresponding to increased autophagic flux, were associated with lower tumor stage, reduced metastasis and improved 5-year survival. These data demonstrate that transcriptional induction of autophagy in ccRCC is accompanied by AMPK/mTOR-independent increase in ULK1 activation and autophagic flux, which might slow tumor progression and metastasis independently of apoptosis.

DUSP4 is an Oncogenic Gene for the Carcinogenesis of Clear cell Renal Cell Carcinoma

2021 ◽  
Author(s):  
Xianyou Zeng ◽  
Changyan Zhu ◽  
Xianxin Zhu
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Renal Cell ◽  
Clear Cell ◽  
Mrna Levels ◽  
Loss Of Function ◽  
Cell Renal Cell Carcinoma ◽  
Cancer Tissues ◽  
Oncogenic Gene

Abstract DUSP4 is considered as an oncogenic gene. However, the effect of DUSP4 on the oncogenesis of Clear cell Renal cell carcinoma (CCRCC) is still unclear. In this study, we explored the expression pattern of DUSP4 in CCRCC cancer tissues and CCRCC cell lines by qRT-PCR. Furthermore, we investigated the roles of DUSP4 in CCRCC using gain-of-function and loss-of-function assays. Here, DUSP4 mRNA levels were significantly increased in CCRCC tissues and cell lines. DUSP4 overexpression promotes the proliferation, migration and tumorigenicity of CCRCC cells while DUSP4 silencing showed the opposite effects. DUSP4 serves as an oncogenic gene in CCRCC carcinogenesis, indicating the potential value of DUSP4 in the diagnosis and treatment of CCRCC.

scholarly journals Early Diagnostic and Prognostic Value of BIRC5 in Clear Cell Renal Cell Carcinoma Based on TCGA Data

2020 ◽  
Author(s):  
Jingyuan Wang ◽  
Min Chen ◽  
Chengxue Dang ◽  
Hao Zhang ◽  
Xin Wang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Early Diagnosis ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Clinicopathological Parameters ◽  
Normal Kidney ◽  
Cell Renal Cell Carcinoma ◽  
Important Indicator ◽  
Early Diagnostic

Abstract Purpose: Clear cell renal cell carcinoma (ccRCC) is a highly lethal cancer that would benefit from non-invasive innovative markers providing early diagnostic and prognostic detection. Increased BIRC5 (baculoviral inhibitor of apoptosis repeat containing 5) expression is associated with negative outcomes or survival in various cancers. Our study aims to investigate the role of BIRC5 of early diagnosis and prognosis in ccRCC by studying the expression of BIRC5 and the correlation between BIRC5 expression and clinicopathological parameters, prognosis in ccRCC. Methods: The BIRC5 expression in ccRCC tissues and normal kidney tissues was measured using the Cancer Genome Atlas (TCGA) database and The Human Protein Atlas database. The correlation between BIRC5 expression and clinicopathological parameters, prognosis in ccRCC was analyzed using UALCAN, Kaplan Meier plotter, GEPIA and SurvExpress. Results: BIRC5 expression is significantly higher in ccRCC than in normal kidney tissues, and is correlated with the clinical stage and pathological grade of ccRCC(P<0.05). The result of analyzing the relationship between BIRC5 expression and outcomes in ccRCC indicates that high BIRC5 expression is an independent prognostic factor affecting overall survival and disease-free survival of ccRCC (P<0.05). Compared with normal kidney tissues, the immunohistochemical test shows that BIRC5 is significantly upregulated in ccRCC tissues. Conclusions: The high expression of BIRC5 is an important indicator of the prognosis of ccRCC, which makes BIRC5 be an effective biomarker for predicting the prognosis of patients in ccRCC. BIRC5 may be a great potential biomarker for early diagnosis of ccRCC.

638: Macroscopic Tumor Necrosis is a Prognostic Indicator for Non-Metastatic Clear Cell Renal Cell Carcinoma

2007 ◽  
Vol 177 (4S) ◽  
pp. 214-214
Author(s):  
Sung Kyu Hong ◽  
Byung Kyu Han ◽  
In Ho Chang ◽  
June Hyun Han ◽  
Ji Hyung Yu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Tumor Necrosis ◽  
Clear Cell ◽  
Prognostic Indicator ◽  
Cell Renal Cell Carcinoma ◽  
Macroscopic Tumor
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