Rb induces a proliferative arrest and curtails Brn-2 expression in retinoblastoma cells.
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 (RbWT) and to a lesser extent the low penetrance mutant Rb661W induced a G0/G1 arrest associated with induction of p27KIP1 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.


CONCLUSIONS
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.
Cobrinik
David
D
Margaret M, Dyson Vision Research Institute, Weill Medical College of Cornell University, New York, NY 10021, USA. dec2014@med.cornell.edu
Francis
Richard O
RO
Abramson
David H
DH
Lee
Thomas C
TC
D045744:Cell Line, Tumor; D049109:Cell Proliferation; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D049452:Green Fluorescent Proteins / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D016086:Lentivirus / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D050809:POU Domain Factors / Q000378:metabolism / Q000502:physiology*; D012175:Retinoblastoma / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000378:metabolism / Q000502:physiology*; D013234:Stem Cells / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic
D018398:Homeodomain Proteins; D050809:POU Domain Factors; D016160:Retinoblastoma Protein; C085076:transcription factor Brn-2; D049452:Green Fluorescent Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27