Related Experiment Video

Updated: May 13, 2026

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
07:25

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer

Published on: March 6, 2018

Gene Expression Profiling Reveals Regulation of ERK Phosphorylation by Androgen-Induced Tumor Suppressor U19/EAF2 in

Fei Su1, Bruna R S Correa, Jianhua Luo

  • 1Department of Urology, University of Pittsburgh, Pittsburgh, PA, 15232, USA.

Cancer Microenvironment : Official Journal of the International Cancer Microenvironment Society
|February 27, 2013
PubMed

Insights

Loss of U19/EAF2 protein in the prostate activates the RAS-BRAF-ERK pathway, promoting cancer. This suggests U19/EAF2 acts as a tumor suppressor by regulating this critical signaling cascade.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Signal Transduction

Background:

  • U19/EAF2, regulated by androgens in the prostate, controls RNA Pol II transcriptional elongation.
  • Inactivation of U19/EAF2 is linked to tumorigenesis, but its tumor suppression mechanism is unclear.

Purpose of the Study:

  • To elucidate the tumor suppressive mechanisms of U19/EAF2.
  • To identify molecular pathways regulated by U19/EAF2 in the mouse prostate.

Main Methods:

  • cDNA microarray analysis to identify U19/EAF2-regulated transcripts.
  • Bioinformatics analysis to predict activated signaling pathways.
  • Quantitative PCR (qPCR), immunostaining, and Western blot to validate gene and protein expression changes.

Main Results:

  • U19/EAF2 knockout identified 164 regulated mRNA transcripts.
  • Bioinformatics analysis revealed activation of the RAS-BRAF-ERK signaling pathway.
  • Increased BRAF mRNA and p-ERK protein levels confirmed pathway activation.
  • Loss of EAF2 up-regulates RAS cascade genes (Grb2, PI3K, BRAF), elevating p-ERK.

Conclusions:

  • Loss of U19/EAF2 activates the RAS-BRAF-ERK pathway, potentially driving prostate carcinogenesis.
  • U19/EAF2 plays a role in the crosstalk between androgen receptor and the RAS-BRAF-ERK pathway.
  • U19/EAF2 functions as a tumor suppressor in the prostate by modulating key oncogenic signaling pathways.

More Related Videos

MicroRNA Detection in Prostate Tumors by Quantitative Real-time PCR (qPCR)08:30

MicroRNA Detection in Prostate Tumors by Quantitative Real-time PCR (qPCR)

Published on: May 16, 2012

An Orthotopic Murine Model of Human Prostate Cancer Metastasis06:48

An Orthotopic Murine Model of Human Prostate Cancer Metastasis

Published on: September 18, 2013

Related Concept Videos

mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...