title: Bigh3 silencing increases retinoblastoma tumor growth in the murine SV40-TAg-Rb model.
abstract: BIGH3, a secreted protein of the extracellular matrix interacts with collagen and integrins on the cell surface. BIGH3 can have opposing functions in cancer, acting either as tumor suppressor or promoter by enhancing tumor progression and angiogenesis. In the eye, BIGH3 is expressed in the cornea and the retinal pigment epithelium and could impact on the development of retinoblastoma, the most common paediatric intraocular neoplasm. Retinoblastoma initiation requires the inactivation of both alleles of the RB1 tumor suppressor gene in the developing retina and tumor progression involves additional genomic changes. To determine whether BIGH3 affects retinoblastoma development, we generated a retinoblastoma mouse model with disruption of the Bigh3 genomic locus. Bigh3 silencing in these mice resulted in enhanced tumor development in the retina. A decrease in apoptosis is involved in the initial events of tumorigenesis, followed by an increased activity of the pro-survival ERK pathway as well as an upregulation of cyclin-dependent kinases (CDKs). Taken together, these data suggest that BIGH3 acts as a tumor suppressor in the retina.
authors.affiliation: IRO - Institute for Research in Ophthalmology, CH-1950 Sion, Switzerland.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Allaman-Pillet
authors.affiliation: IRO - Institute for Research in Ophthalmology, CH-1950 Sion, Switzerland.
authors.forename: Anne
authors.initials: A
authors.lastname: Oberson
authors.affiliation: IRO - Institute for Research in Ophthalmology, CH-1950 Sion, Switzerland.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Schorderet
mesh_terms: D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics*; D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D019572:Retinal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D055213:Retinal Pigment Epithelium / Q000378:metabolism / Q000473:pathology; D012175:Retinoblastoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism; D047368:Tumor Burden / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D000099222:betaIG-H3 Protein
chemical_list: D000952:Antigens, Polyomavirus Transforming; D018844:Cyclin-Dependent Kinases; D016326:Extracellular Matrix Proteins; D016160:Retinoblastoma Protein; D016212:Transforming Growth Factor beta; D025521:Tumor Suppressor Proteins; D000099222:betaIG-H3 Protein
keywords: BIGH3; SV40-TAg-Rb mice; cancer; retinoblastoma