Research Abstracts Online
January 2010 - March 2011
University of Minnesota Twin Cities
PI: Timothy C. Hallstrom
Regulation of Rb/E2F Apoptosis
Most cancers arise when cells sustain oncogenic mutations that drive proliferation and secondary mutations that block oncogene induced apoptosis. The retinoblastoma gene (Rb) is one of the most commonly mutated tumor suppressors in cancer. The retinoblastoma protein (pRb) regulates cell cycle progression and tumorigenesis through its repression of a family of transcription factors called E2Fs. The E2F family of transcription factors, which become deregulated in human cancers that have lost pRb function, normally promote expression of genes involved in cell cycle division and proliferation. E2Fs also paradoxically promote expression of apoptosis inducing genes like p53 as a mechanism to eliminate incipient cancer cells. Many of the E2F1 regulated apoptosis inducing genes are tumor suppressors mutated in various cancers. The goals of this project are: to identify which genes control Rb/E2F1 induced apoptosis; to test whether defects in these regulons lead to tumorigenesis; and to determine if this knowledge can be used to enhance current chemotherapy.
To this end, these researchers are utilizing genome-wide short-hairpin RNA (shRNA) library technology to screen for regulators of E2F1-induced apoptosis. They use MSI resources for sequence analysis.
Xudong Liang, Research Associate
Huarui Lu, Research Associate