RGD Reference Report - Divergent roles for RalA and RalB in malignant growth of human pancreatic carcinoma cells. - Rat Genome Database

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Divergent roles for RalA and RalB in malignant growth of human pancreatic carcinoma cells.

Authors: Lim, Kian-Huat  O'Hayer, Kevin  Adam, Stacey J  Kendall, S Disean  Campbell, Paul M  Der, Channing J  Counter, Christopher M 
Citation: Lim KH, etal., Curr Biol. 2006 Dec 19;16(24):2385-94. doi: 10.1016/j.cub.2006.10.023.
RGD ID: 14394417
Pubmed: PMID:17174914   (View Abstract at PubMed)
DOI: DOI:10.1016/j.cub.2006.10.023   (Journal Full-text)


BACKGROUND: The Ral guanine nucleotide-exchange factors (RalGEFs) serve as key effectors for Ras oncogene transformation of immortalized human cells. RalGEFs are activators of the highly related RalA and RalB small GTPases, although only the former has been found to promote Ras-mediated growth transformation of human cells. In the present study, we determined whether RalA and RalB also had divergent roles in promoting the aberrant growth of pancreatic cancers, which are characterized by the highest occurrence of Ras mutations.
RESULTS: We now show that inhibition of RalA but not RalB expression universally reduced the transformed and tumorigenic growth in a panel of ten genetically diverse human pancreatic cancer cell lines. Despite the apparent unimportant role of RalB in tumorigenic growth, it was nevertheless critical for invasion in seven of nine pancreatic cancer cell lines and for metastasis as assessed by tail-vein injection of three different tumorigenic cell lines tested. Moreover, both RalA and RalB were more commonly activated in pancreatic tumor tissue than other Ras effector pathways.
CONCLUSIONS: RalA function is critical to tumor initiation, whereas RalB function is more important for tumor metastasis in the tested cell lines and thus argues for critical, but distinct, roles of Ral proteins during the dynamic progression of Ras-driven pancreatic cancers.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
RALBHumanpancreatic adenocarcinoma treatmentIMP human cells in a mouse modelRGD 
RalbRatpancreatic adenocarcinoma treatmentISORALB (Homo sapiens)human cells in a mouse modelRGD 
RalbMousepancreatic adenocarcinoma treatmentISORALB (Homo sapiens)human cells in a mouse modelRGD 

Objects Annotated

Genes (Rattus norvegicus)
Ralb  (RAS like proto-oncogene B)

Genes (Mus musculus)
Ralb  (v-ral simian leukemia viral oncogene B)

Genes (Homo sapiens)
RALB  (RAS like proto-oncogene B)


Additional Information