RGD Reference Report - PTEN-deficient cancers depend on PIK3CB. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models   new Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources

PTEN-deficient cancers depend on PIK3CB.

Authors: Wee, Susan  Wiederschain, Dmitri  Maira, Sauveur-Michel  Loo, Alice  Miller, Christine  deBeaumont, Rosalie  Stegmeier, Frank  Yao, Yung-Mae  Lengauer, Christoph 
Citation: Wee S, etal., Proc Natl Acad Sci U S A. 2008 Sep 2;105(35):13057-62. doi: 10.1073/pnas.0802655105. Epub 2008 Aug 28.
RGD ID: 13217420
Pubmed: PMID:18755892   (View Abstract at PubMed)
PMCID: PMC2529105   (View Article at PubMed Central)
DOI: DOI:10.1073/pnas.0802655105   (Journal Full-text)

Deregulation of the PI3K signaling pathway is observed in many human cancers and occurs most frequently through loss of PTEN phosphatase tumor suppressor function or through somatic activating mutations in the Class IA PI3K, PIK3CA. Tumors harboring activated p110alpha, the protein product of PIK3CA, require p110alpha activity for growth and survival and hence are expected to be responsive to inhibitors of its lipid kinase activity. Whether PTEN-deficient cancers similarly depend on p110alpha activity to sustain activation of the PI3K pathway has been unclear. In this study, we used a single-vector lentiviral inducible shRNA system to selectively inactivate the three Class IA PI3Ks, PIK3CA, PIK3CB, and PIK3CD, to determine which PI3K isoforms are responsible for driving the abnormal proliferation of PTEN-deficient cancers. Down-regulation of PIK3CA in colorectal cancer cells harboring mutations in PIK3CA inhibited downstream PI3K signaling and cell growth. Surprisingly, PIK3CA depletion affected neither PI3K signaling nor cell growth in 3 PTEN-deficient cancer cell lines. In contrast, down-regulation of the PIK3CB isoform, which encodes p110beta, resulted in pathway inactivation and subsequent inhibition of growth in both cell-based and in vivo settings. This essential function of PIK3CB in PTEN-deficient cancer cells required its lipid kinase activity. Our findings demonstrate that although p110alpha activation is required to sustain the proliferation of established PIK3CA-mutant tumors, PTEN-deficient tumors are dependent instead on p110beta signaling. This unexpected finding demonstrates the need to tailor therapeutic approaches to the genetic basis of PI3K pathway activation to achieve optimal treatment response.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
prostate adenocarcinoma treatmentIMP 13217420 RGD 
prostate adenocarcinoma treatmentISOPIK3CB (Homo sapiens)13217420; 13217420 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Pik3cb  (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit beta)

Genes (Mus musculus)
Pik3cb  (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta)

Genes (Homo sapiens)
PIK3CB  (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta)


Additional Information