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1.
Br J Cancer ; 108(4): 973-82, 2013 Mar 05.
Article En | MEDLINE | ID: mdl-23299537

BACKGROUND: The B-cell translocation gene 2 (BTG2) is considered to act as a tumour-suppressor gene because of its antiproliferative and antimigratory activities. Higher levels of BTG2 expression in tumour cells have been linked to a better clinical outcome for several cancer entities. Here, we investigated the expression and function of BTG2 in bladder cancer. METHODS: The expression of BTG2 in bladder cancer cells was silenced by RNA interference. Cell motility was investigated by wound healing and Boyden chamber assays. The protein expression of BTG2 in bladder cancer was studied by immunohistochemistry. RESULTS: We observed that targeted suppression of BTG2 by RNA interference did not result in growth stimulation but led to a substantial inhibition of bladder cancer cell motility. Tissue microarray analyses of bladder cancer cystectomy specimens revealed that higher BTG2 expression levels within the tumours correlated strongly with a decreased cancer-specific survival for bladder cancer patients. CONCLUSION: These results indicate that endogenous BTG2 expression contributes to the migratory potential of bladder cancer cells. Moreover, high levels of BTG2 in bladder cancers are linked to decreased cancer-specific survival. These findings question the conception that BTG2 generally acts as a tumour suppressor and typically represents a favourable clinical marker for cancer patients.


Immediate-Early Proteins/genetics , Tumor Suppressor Proteins/genetics , Urinary Bladder Neoplasms/genetics , Aged , Cell Line, Tumor , Cell Movement/genetics , Female , Genes, Tumor Suppressor , Humans , Immediate-Early Proteins/metabolism , Middle Aged , RNA Interference , Retrospective Studies , Tumor Suppressor Proteins/metabolism , Urinary Bladder Neoplasms/mortality
2.
Anal Biochem ; 410(2): 161-70, 2011 Mar 15.
Article En | MEDLINE | ID: mdl-21059336

Protein microarrays represent an emerging technology that promises to facilitate high-throughput proteomics. The major goal of this technology is to employ peptides, full-length proteins, antibodies, and small molecules to simultaneously screen thousands of targets for potential protein-protein interactions or modifications of the proteome. This article describes the performance of a set of peptide aptamers specific for the human papillomavirus (HPV) type 16 oncoproteins E6 and E7 in a microarray format. E6 and E7 peptide aptamer microarrays were probed with fluorescence-labeled lysates generated from HPV-infected cervical keratinocytes expressing both E6 and E7 oncoproteins. Peptide aptamer microarrays are shown to detect low levels of E6 and E7 proteins. Peptide aptamers specific for cellular proteins included on these microarrays suggested that expression of CDK2, CDK4, and BCL-6 may be affected by HPV infection and genome integration. We conclude that peptide aptamer microarrays represent a promising tool for proteomics and may be of value in biological and clinical investigations of cervical carcinogenesis.


Aptamers, Peptide/analysis , Cell Extracts/chemistry , High-Throughput Screening Assays/methods , Human papillomavirus 16/isolation & purification , Oncogene Proteins, Viral/analysis , Protein Array Analysis/methods , Repressor Proteins/analysis , Aptamers, Peptide/chemistry , Aptamers, Peptide/metabolism , Cell Line , Cell Line, Tumor , Female , Humans , Keratinocytes , Oncogene Proteins/chemistry , Oncogene Proteins/metabolism , Papillomavirus E7 Proteins/chemistry , Papillomavirus E7 Proteins/metabolism , Papillomavirus Infections/virology , Uterine Cervical Neoplasms/virology
3.
Br J Cancer ; 97(9): 1271-6, 2007 Nov 05.
Article En | MEDLINE | ID: mdl-17968430

The antiapoptotic Livin/ML-IAP gene has recently gained much attention as a potential new target for cancer therapy. Reports indicating that livin is expressed almost exclusively in tumours, but not in the corresponding normal tissue, suggested that the targeted inhibition of livin may present a novel tumour-specific therapeutic strategy. Here, we compared the expression of livin in renal cell carcinoma and in non-tumorous adult kidney tissue by quantitative real-time reverse transcription-PCR, immunoblotting, and immunohistochemistry. We found that livin expression was significantly increased in tumours (P=0.0077), but was also clearly detectable in non-tumorous adult kidney. Transcripts encoding Livin isoforms alpha and beta were found in both renal cell carcinoma and normal tissue, without obvious qualitative differences. Livin protein in renal cell carcinoma samples exhibited cytoplasmic and/or nuclear staining. In non-tumorous kidney tissue, Livin protein expression was only detectable in specific cell types and restricted to the cytoplasm. Thus, whereas the relative overexpression of livin in renal cell carcinoma indicates that it may still represent a therapeutic target to increase the apoptotic sensitivity of kidney cancer cells, this strategy is likely to be not tumour-specific.


Adaptor Proteins, Signal Transducing/genetics , Apoptosis , Biomarkers, Tumor/genetics , Carcinoma, Renal Cell/genetics , Gene Expression Regulation, Neoplastic , Inhibitor of Apoptosis Proteins/genetics , Kidney Neoplasms/genetics , Kidney/metabolism , Neoplasm Proteins/genetics , Adaptor Proteins, Signal Transducing/metabolism , Biomarkers, Tumor/metabolism , Carcinoma, Renal Cell/metabolism , Humans , Immunoenzyme Techniques , Inhibitor of Apoptosis Proteins/metabolism , Kidney Neoplasms/metabolism , Neoplasm Proteins/metabolism , RNA, Neoplasm/genetics , RNA, Neoplasm/metabolism , Reverse Transcriptase Polymerase Chain Reaction
4.
J Clin Exp Neuropsychol ; 26(6): 846-56, 2004 Sep.
Article En | MEDLINE | ID: mdl-15370380

The Tower of London (ToL) test is widely used for measuring planning and aspects of problem solving. The primary focus of this study was to asses the relationship among different measures on the ToL. A secondary purpose was to examine the putative relationship between intelligence and working memory with that of ToL performance. Analyses of the interrelation of several ToL parameters indicated that better ToL performance was associated with longer preplanning time and shorter movement execution time. Good performers showed a stronger increase in preplanning duration with task difficulty then intermediate or poor planners. Stepwise multiple regression analysis yield fluid intelligence as the only significant predictor of ToL performance. These result suggest that the Tower of London assesses predominantly planning and problem solving and could not be explained by other cognitive domains.


Cognition/physiology , Mental Processes/physiology , Neuropsychological Tests , Problem Solving/physiology , Weights and Measures , Adult , Analysis of Variance , Female , Humans , Intelligence/physiology , Male , Memory, Short-Term/physiology , Reaction Time , Regression Analysis , Task Performance and Analysis , Time Factors , Verbal Learning/physiology
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