RGD Reference Report - Expression of ral GTPases, their effectors, and activators in human bladder cancer. - Rat Genome Database

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Expression of ral GTPases, their effectors, and activators in human bladder cancer.

Authors: Smith, SC  Oxford, G  Baras, AS  Owens, C  Havaleshko, D  Brautigan, DL  Safo, MK  Theodorescu, D 
Citation: Smith SC, etal., Clin Cancer Res. 2007 Jul 1;13(13):3803-13.
RGD ID: 2324917
Pubmed: PMID:17606711   (View Abstract at PubMed)
DOI: DOI:10.1158/1078-0432.CCR-06-2419   (Journal Full-text)

PURPOSE: The Ral family of small G proteins has been implicated in tumorigenesis, invasion, and metastasis in in vitro and animal model systems; however, a systematic evaluation of the state of activation, mutation, or expression of these GTPases has not been reported in any tumor type. EXPERIMENTAL DESIGN: We determined the activation state of the RalA and RalB paralogs in 10 bladder cancer cell lines with varying Ras mutation status. We sequenced RalA and RalB cDNAs from 20 bladder cancer cell lines and functionally evaluated the mutations found. We determined the expression of Ral, Ral activators, and Ral effectors on the level of mRNA or protein in human bladder cancer cell lines and tissues. RESULTS: We uncovered one E97Q substitution mutation of RalA in 1 of 20 cell lines tested and higher Ral activation in cells harboring mutant HRAS. We found overexpression of mRNAs for RalA and Aurora-A, a mitotic kinase that activates RalA, in bladder cancer (both P < 0.001), and in association with tumors of higher stage and grade. RalBP1, a canonical Ral effector, mRNA and protein was overexpressed in bladder cancer (P < 0.001), whereas Filamin A was underexpressed (P = 0.004). We determined that RalA mRNA levels correlated significantly with protein levels (P < 0.001) and found protein overexpression of both GTPases in homogenized invasive cancers. Available data sets suggest that RalA mRNA is also overexpressed in seminoma, glioblastoma, and carcinomas of the liver, pancreas, and prostate. CONCLUSION: These findings of activation and differential expression of RalA and RalB anchor prior work in model systems to human disease and suggest therapeutic strategies targeting both GTPases in this pathway may be beneficial.



RGD Manual Disease Annotations    Click to see Annotation Detail View
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
RALBP1Humanurinary bladder cancer  IEP mRNA and protein:increased expression:urinary bladderRGD 
Ralbp1Raturinary bladder cancer  ISORALBP1 (Homo sapiens)mRNA and protein:increased expression:urinary bladderRGD 
Ralbp1Mouseurinary bladder cancer  ISORALBP1 (Homo sapiens)mRNA and protein:increased expression:urinary bladderRGD 

Objects Annotated

Genes (Rattus norvegicus)
Ralbp1  (ralA binding protein 1)

Genes (Mus musculus)
Ralbp1  (ralA binding protein 1)

Genes (Homo sapiens)
RALBP1  (ralA binding protein 1)


Additional Information