pRb-Independent Growth Arrest and Transcriptional Regulation of E2F Target Genes

Abstract

The retinoblastoma tumor suppressor (pRb) has traditionally been studied as a negative regulator of cell cycle progression through its interactions with the E2F family of transcription factors. Utilizing prostate epithelial cell lines established from Rb+/+ and Rb-/- prostate tissues, we previously demonstrated that Rb-/- epithelial cells were not transformed and retained the ability to differentiate in vivo despite the lack of pRb. To further study the effects of pRb loss in an epithelial cell population, we utilized oligonucleotide microarrays to identify any pRb-dependent transcriptional regulation during serum depletioninduced growth arrest. These studies identified 120 unique transcripts regulated by growth arrest in Rb+/+ cells. In these wild-type cells, the majority (80%) of altered transcripts were downregulated, including 40 previously identified E2F target genes. Although the transcriptional repression of E2F target genes is characteristic of pRb pocket protein family activity, further analysis revealed that, compared to Rb+/+ cells, Rb-/- cells exhibited a nearly identical response for all transcripts including those of E2F target genes. These findings demonstrate that pRb is not strictly required for the vast majority of transcriptional alterations associated with growth arrest.

Keywords

• Retinoblastoma
• pRb
• E2F
• microarray
• prostate