Oncotarget

Research Papers:

Bigh3 silencing increases retinoblastoma tumor growth in the murine SV40-TAg-Rb model

Nathalie Allaman-Pillet _, Anne Oberson and Daniel F. Schorderet

PDF  |  HTML  |  Supplementary Files  |  How to cite

Oncotarget. 2017; 8:15490-15506. https://doi.org/10.18632/oncotarget.14659

Metrics: PDF 2297 views  |   HTML 2482 views  |   ?  


Abstract

Nathalie Allaman-Pillet1, Anne Oberson1, Daniel F. Schorderet1

1IRO - Institute for Research in Ophthalmology, CH-1950 Sion, Switzerland

Correspondence to:

Nathalie Allaman-Pillet, email: [email protected]

Keywords: BIGH3, retinoblastoma, cancer, SV40-TAg-Rb mice

Received: May 31, 2016     Accepted: December 24, 2016     Published: January 14, 2017

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.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 14659