Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of human stage 1,2 normal and tumor kidney cancer


ABSTRACT: Although renal cell carcinoma (RCC) is the sixth-leading cause of cancer death, the molecular events leading to disease onset and progression are not well understood. Genomic profiling of clear cell RCC (cRCC) patients indicated that loss of a negative regulator of the Wnt pathway, secreted frizzled-related protein 1 (sFRP1), occurred in the majority of more than 100 patients tested. To our knowledge, this is the first report of loss of sFRP1 expression in patients diagnosed with cRCC; this loss occurs in early stage cRCC, suggesting that it may be an important early event in renal carcinogenesis. Genomic profiling of patient matched normal and cRCC tissues identified Wnt regulated genes to be aberrantly increased in cRCC tissues suggesting sFRP1 suppresses Wnt signaling in cRCC. In order to test the hypothesis that sFRP1 acts as a tumor suppressor in cRCC, we have stably expressed sFRP1 in cRCC cells. sFRP1 expression in cRCC cells resulted in decreased growth in cell culture, inhibition of anchorage-independent growth, and decreased tumor volume in a nude mouse model. Together these data suggest an important role for sFRP1 as a tumor suppressor in cRCC. Experiment Overall Design: 5pts on Stg1 Normal and Tumor and 5pts on Stg2 normal and tumor each Experiment Overall Design: Additional information may be found in the following supplementary files: Experiment Overall Design: 1) GSE6344_Combofiles.zip - contains all text files for combination tables. Experiment Overall Design: 2) GSE6344_Dataframe.TXT - contains the Dataframe after filters and normalizations for differential testing. Experiment Overall Design: 3) GSE6344_MethodsDetails.PDF - describes the steps for creating the combination tables from HG-U133 A, B set and also the method for normalizations and filters. Experiment Overall Design: 4) GSE6344_a1way_StageTumor_@95(@99).txt - contain results from Anova 1 way at p-values<=0.05 and 0.01.

ORGANISM(S): Homo sapiens

SUBMITTER: John Copland 

PROVIDER: E-GEOD-6344 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Secreted frizzled-related protein 1 loss contributes to tumor phenotype of clear cell renal cell carcinoma.

Gumz Michelle L ML   Zou Hongzhi H   Kreinest Pamela A PA   Childs April C AC   Belmonte Leandra S LS   LeGrand Shauna N SN   Wu Kevin J KJ   Luxon Bruce A BA   Sinha Mala M   Parker Alexander S AS   Sun L-Z LZ   Ahlquist David A DA   Wood Christopher G CG   Copland John A JA  

Clinical cancer research : an official journal of the American Association for Cancer Research 20070801 16


<h4>Purpose</h4>Incidence and mortality rates for renal cell carcinoma (RCC) have been rising for decades. Unfortunately, the molecular events that support RCC carcinogenesis remain poorly understood. In an effort to gain a better understanding of signaling events in clear cell RCC (cRCC), we investigated the antitumor activity of secreted frizzled-related protein 1 (sFRP1), a negative regulator of Wnt signaling.<h4>Experimental design</h4>Genomic profiling of cRCC tumors and patient-matched nor  ...[more]

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