Academic Commons

Articles

Rb induces a proliferative arrest and curtails Brn-2 expression in retinoblastoma cells

Cobrinik, David; Francis, Richard Oscar; Abramson, David H.; Lee, Thomas C.

Background: Retinoblastoma is caused by loss of the Rb protein in early retinal cells. Although numerous Rb functions have been identified, Rb effects that specifically relate to the suppression of retinoblastoma have not been defined. Results: In this study, we examined the effects of restoring Rb to Y79 retinoblastoma cells, using novel retroviral and lentiviral vectors that co-express green fluorescent protein (GFP). The lentiviral vector permitted transduction with sufficient efficiency to perform biochemical analyses. Wild type Rb (Rb^(WT)) and to a lesser extent the low penetrance mutant Rb^(661W) induced a G0/G1 arrest associated with induction of p27^(KIP1) and repression of cyclin E1 and cyclin E2. Microarray analyses revealed that in addition to down-regulating E2F-responsive genes, Rb repressed expression of Brn-2 (POU3F2), which is implicated as an important transcriptional regulator in retinal progenitor cells and other neuroendocrine cell types. The repression of Brn-2 was a specific Rb effect, as ectopic p27 induced a G0/G1 block, but enhanced, rather than repressed, Brn-2 expression. Conclusion: In addition to Rb effects that occur in many cell types, Rb regulates a gene that selectively governs the behavior of late retinal progenitors and related cells.

Files

Also Published In

Title
Molecular Cancer
DOI
https://doi.org/10.1186/1476-4598-5-72

More About This Work

Academic Units
Pathology and Cell Biology
Published Here
September 9, 2014
Academic Commons provides global access to research and scholarship produced at Columbia University, Barnard College, Teachers College, Union Theological Seminary and Jewish Theological Seminary. Academic Commons is managed by the Columbia University Libraries.