Common ELF1 deletion in prostate cancer bolsters oncogenic ETS function, inhibits senescence and promotes docetaxel resistance.

ETS family transcription factors play major roles in prostate tumorigenesis with some acting as oncogenes and others as tumor suppressors. ETS factors can compete for binding at some cis-regulatory sequences, but display specific binding at others. Therefore, changes in expression of ETS family members during tumorigenesis can have complex, multimodal effects.

Therapeutic Targeting of TFE3/IRS-1/PI3K/mTOR Axis in Translocation Renal Cell Carcinoma.

Purpose: Translocation renal cell carcinoma (tRCC) represents a rare subtype of kidney cancer associated with various , or gene fusions that are not responsive to standard treatments for RCC. Therefore, the identification of new therapeutic targets represents an unmet need for this disease.

Experimental Design: We have established and characterized a tRCC patient-derived xenograft, RP-R07, as a novel preclinical model for drug development by using next-generation sequencing and bioinformatics analysis.

Extracellular signal-regulated kinase signaling regulates the opposing roles of JUN family transcription factors at ETS/AP-1 sites and in cell migration.

JUN transcription factors bind DNA as part of the AP-1 complex, regulate many cellular processes, and play a key role in oncogenesis. The three JUN proteins (c-JUN, JUNB, and JUND) can have both redundant and unique functions depending on the biological phenotype and cell type assayed. Mechanisms that allow this dynamic switching between overlapping and distinct functions are unclear.

ETS1 is a genome-wide effector of RAS/ERK signaling in epithelial cells.

The RAS/ERK pathway is commonly activated in carcinomas and promotes oncogenesis by altering transcriptional programs. However, the array of cis-regulatory elements and trans-acting factors that mediate these transcriptional changes is still unclear. Our genome-wide analysis determined that a sequence consisting of neighboring ETS and AP-1 transcription factor binding sites is enriched near cell migration genes activated by RAS/ERK signaling in epithelial cells.

Prostate cancer ETS rearrangements switch a cell migration gene expression program from RAS/ERK to PI3K/AKT regulation.

Background: The RAS/ERK and PI3K/AKT pathways induce oncogenic gene expression programs and are commonly activated together in cancer cells. Often, RAS/ERK signaling is activated by mutation of the RAS or RAF oncogenes, and PI3K/AKT is activated by loss of the tumor suppressor PTEN. In prostate cancer, PTEN deletions are common, but, unlike other carcinomas, RAS and RAF mutations are rare.

Oncogenic ETS proteins mimic activated RAS/MAPK signaling in prostate cells.

The aberrant expression of an oncogenic ETS transcription factor is implicated in the progression of the majority of prostate cancers, 40% of melanomas, and most cases of gastrointestinal stromal tumor and Ewing's sarcoma. Chromosomal rearrangements in prostate cancer result in overexpression of any one of four ETS transcription factors. How these four oncogenic ETS genes differ from the numerous other ETS genes expressed in normal prostate and contribute to tumor progression is not understood.

The ETS gene ETV4 is required for anchorage-independent growth and a cell proliferation gene expression program in PC3 prostate cells.

Chromosomal abnormalities that give rise to elevated expression levels of the ETS genes ETV1, ETV4, ETV5, or ERG are prevalent in prostate cancer, but the function of these transcription factors in carcinogenesis is not clear. Previous work in cell lines implicates ERG, ETV1, and ETV5 as regulators of invasive growth but not transformation. Here we show that the PC3 prostate cancer cell line provides a model system to study the over-expression of ETV4.

Global effect of PEG-IFN-alpha and ribavirin on gene expression in PBMC in vitro.

Using oligonucleotide microarrays, we have examined the expression of 22,000 genes in peripheral blood cells treated with pegylated interferon-alpha2b (PEG-IFN-alpha) and ribavirin. Treatment with ribavirin had very little effect on gene expression, whereas treatment with PEG-IFN-alpha had a dramatic effect, modulating the expression of approximately 1000 genes (at p < 0.001).