The prognostic value of cyclin D1 in renal cell carcinoma

Lima, Marcela Sampaio; Pereira, Renan Augusto; Costa, R. S.; Tucci, Sílvio; Dantas, Márcio; Muglia, Valdair Francisco; Ravinal, Roberto Cuan; Barros-Silva, Gyl Eanes

doi:10.1007/s11255-013-0602-0

Cited by 28 publications

(17 citation statements)

References 16 publications

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“…In renal cell cancer, CCND1 was absent in normal kidney samples but overexpressed in RCC. High CCND1 expression was related to good clinical outcome and to most known favorable prognostic factors [29]. Moreover, high CCND3 protein was observed in 16% of the tumors and was significantly associated with high TNM stage, high nuclear grade, high proliferation and young age [30].…”

Section: Discussionmentioning

confidence: 99%

The Silencing of CCND2 by Promoter Aberrant Methylation in Renal Cell Cancer and Analysis of the Correlation between CCND2 Methylation Status and Clinical Features

et al. 2016

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Cyclin D2 (CCND2) is a member of the D-type cyclins, which plays a pivotal role in cell cycle regulation, differentiation and malignant transformation. However, its expression status and relative regulation mechanism remains unclear in renal cell cancer (RCC). In our study, the mRNA expression level of CCND2 is down-regulated in 22/23 paired RCC tissues (p<0.05). In addition, its protein expression level is also decreased in 43/43 RCC tumor tissues compared with its corresponding non-malignant tissues (p<0.001). We further detected that CCND2 was down-regulated or silenced in 6/7 RCC cell lines, but expressed in “normal” human proximal tubular (HK-2) cell line. Subsequently, MSP and BGS results showed that the methylation status in CCND2 promoter region is closely associated with its expression level in RCC cell lines. Treatment with 5-Aza with or without TSA restored CCND2 expression in several methylated RCC cell lines. Among the 102 RCC tumors, methylation of CCND2 was detected in 29/102 (28%) cases. Only 2/23 (8.7%) adjacent non-malignant tissues showed methylation. We then analyzed the correlation of clinical features and its promoter methylation. Collectively, our data suggested that loss of CCND2 expression is closely associated with the promoter aberrant methylation.

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Section: Discussionmentioning

confidence: 99%

The Silencing of CCND2 by Promoter Aberrant Methylation in Renal Cell Cancer and Analysis of the Correlation between CCND2 Methylation Status and Clinical Features

et al. 2016

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“…Hedberg et al [31] examined the protein contents in tissues of human ccRCC, and overexpression of Cyclin D1 and Cyclin E were observed. Similarly, Lima et al [32] and Nauman et al [33] showed the high levels of Cyclin D1 and Cyclin E protein in human ccRCC. in cell experiments, researchers found that decreased Cyclin D1 and Cyclin E could inhibit the proliferation of RCC cells [34,35].…”

Section: Discussionmentioning

confidence: 81%

Overexpression of BTG2 suppresses growth, migration, and invasion of human renal carcinoma cells in vitro

Sima¹,

Zhang²,

Sima³

et al. 2016

neo

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The objective of the study was to investigate the impact of BTG2 on growth, migration and invasion of human clear cell renal cell carcinoma (ccRCC) cells. Endogenous expression of BTG2 was evaluated in the ccRCC cell lines (Caki-1, 786-O and Caki-2) and noncancerous human renal proximal tubular cell lines (HKC, HK-2 and RPTEC). BTG2 expression was decreased in the ccRCC cells compared with the noncancerous cells (P < 0.01). Then Caki-1 and 786-O cells described as suitable transfection hosts were used in transfection to carry out biological function studies. The three experimental groups were as follows: BTG2-ORF (transfected with BTG2-ORF plasmid), blank-Vector (transfected with pCMV6-Entry), and Cell-alone group (no DNA transfected in). BTG2 expression in the BTG2-ORF groups was significantly higher than that in the controls (P < 0.01). Cell growth was remarkably reduced and the number of migrating or invading cells was reduced in the BTG2-ORF groups compared with the controls (P < 0.01). Furthermore, Matrix Metalloproteinase-9 (MMP-9), Cyclin D1 and Cyclin E expression were reduced in the BTG2-ORF groups compared with the controls. Here, we have provided data for attenuated BTG2 expression in the ccRCC cells. Overexpressed BTG2 could inhibit cell proliferation, migration and invasion of human ccRCC, and the suppressive effects might be due to down-regulation of MMP-9, Cyclin D1 and Cyclin E expression.

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“…higher levels of cyclin D1 are correlated with tumor size, Fuhrman grade and indicate poor prognosis for patients. 35 Elevated expression of cyclin E was observed in ccRCC tumors; level of cyclin E is correlated with loss of differentiation, increased aneuploidy and higher tumor grade. 36,37 As could be predicted, faster proliferating cells with silenced GRHL2 expression have reduced levels of cell cycle inhibitors p21 and p27.…”

Section: Discussionmentioning

confidence: 98%

Potential protective role of Grainyhead‐like genes in the development of clear cell renal cell carcinoma

Pawlak

Kikulska

Wrzesiński

et al. 2017

Molecular Carcinogenesis

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The involvement of Grainyhead-like (GRHL) transcription factors in various cancers is well documented. However, little is known about their role in clear cell renal cell carcinoma (ccRCC). We discovered that the expression of two of these factors-GRHL1 and GRHL2-are downregulated in ccRCC samples, and their expression is correlated with the expression of VHL gene. This suggests a functional link between the GRHL transcription factors and one of the best known tumor suppressors. Although the GRHL genes are not mutated in ccRCC, some of the single nucleotide polymorphisms in these genes may indicate an increased risk of ccRCC development and/or may allow to assess patients' prognoses and predict their responses to various forms of therapy. Silencing of GRHL2 expression in non-tumorigenic kidney cell line results in increased cell proliferation, increased resistance to apoptosis, as well as changes in the levels of selected proteins involved in the pathogenesis of ccRCC. These changes support the potential role for GRHL2 as a suppressor of ccRCC.

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The prognostic value of cyclin D1 in renal cell carcinoma

Cited by 28 publications

References 16 publications

The Silencing of CCND2 by Promoter Aberrant Methylation in Renal Cell Cancer and Analysis of the Correlation between CCND2 Methylation Status and Clinical Features

The Silencing of CCND2 by Promoter Aberrant Methylation in Renal Cell Cancer and Analysis of the Correlation between CCND2 Methylation Status and Clinical Features

Overexpression of BTG2 suppresses growth, migration, and invasion of human renal carcinoma cells in vitro

Potential protective role of Grainyhead‐like genes in the development of clear cell renal cell carcinoma

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