6533b832fe1ef96bd129a56d

RESEARCH PRODUCT

Effects of PPARγ agonists on the expression of leptin and vascular endothelial growth factor in breast cancer cells.

Marianna TerrasiViviana BazanStefano CarusoLavinia InsalacoValeria AmodeoDaniele FanaleLidia Rita CorsiniC ContaldoA MercantiE FiorioGiuseppe Lo ReGiuseppe CiceroE SurmaczAntonio RussoGiuseppe Lo Re

subject

LeptinVascular Endothelial Growth Factor APhysiologySettore MED/06 - Oncologia MedicaClinical BiochemistryLigandschemistry.chemical_compoundCell MovementPromoter Regions Geneticskin and connective tissue diseasesReceptorGENE-EXPRESSIONLeptindigestive oral and skin physiologyVEGFGene Expression Regulation NeoplasticVascular endothelial growth factorROSIGLITAZONEACTIVATED-RECEPTOR-GAMMAMCF-7 CellsPIOGLITAZONEFemalemedicine.medical_specialtyCell SurvivalSp1 Transcription FactorBLADDER-CANCERBreast NeoplasmsBiologyBenzophenonesBreast cancerCiglitazoneInternal medicinemedicineHumansRNA MessengerViability assayBinding SitesLeptin receptorDose-Response Relationship DrugCell BiologyIN-VITROmedicine.diseaseTRANSACTIVATIONDIABETIC-PATIENTSPPAR gammaEndocrinologychemistryTyrosineTHIAZOLIDINEDIONESACTIVATED-RECEPTOR-GAMMA; BLADDER-CANCER; IN-VITRO; DIABETIC-PATIENTS; GENE-EXPRESSION; VEGF; PIOGLITAZONE; THIAZOLIDINEDIONES; TRANSACTIVATION; ROSIGLITAZONEHormone

description

The obesity hormone leptin has been implicated in breast cancer development. Breast cancer cells express the leptin receptor and are able to synthesize leptin in response to obesity-related stimuli. Furthermore, leptin is a positive regulator of vascular endothelial growth factor (VEGF) and high levels of both proteins are associated with worse prognosis in breast cancer patients. Peroxisome proliferator-activated receptor γ (PPARγ) ligands are therapeutic agents used in patient with Type 2 diabetes and obesity which have recently been studied for their potential anti-tumor effect. Here, we studied if these compounds, ciglitazone and GW1929, can affect the expression of leptin and VEGF in breast cancer cells. In MDA-MB-231 and MCF-7 breast cancer cells, treatment with submolar concentrations of ciglitazone and GW1929 elevated the expression of leptin and VEGF mRNA and protein, and increased cell viability and migration. These effects coincided with increased recruitment of PPARγ to the proximal leptin promoter and decreased association of a transcriptional factor Sp1 with this DNA region.

10.1002/jcp.24295http://hdl.handle.net/10447/74733