Related Experiment Video

Updated: Oct 7, 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

A mechanism for androgen receptor-mediated prostate cancer recurrence after androgen deprivation therapy

C W Gregory1, B He, R T Johnson

  • 1Laboratory for Reproductive Biology, Department of Pediatrics, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA.

Cancer Research
|June 5, 2001
PubMed

Insights

Recurrent prostate cancers often rely on the androgen receptor (AR) for growth. Overexpressed coactivators enhance AR activity, driving tumor recurrence after androgen deprivation therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Endocrinology

Background:

  • Prostate cancer growth is driven by the androgen receptor (AR) and its ligand, dihydrotestosterone.
  • Androgen deprivation therapy (ADT) initially shrinks tumors but often leads to recurrence.
  • The role of AR in mediating recurrent prostate cancer growth remains a critical question.

Purpose of the Study:

  • To investigate the role of the androgen receptor (AR) in recurrent prostate cancer.
  • To identify molecular mechanisms driving tumor regrowth after ADT.

Main Methods:

  • Analysis of androgen receptor (AR) and coactivator expression in recurrent prostate cancers.
  • Assessing the impact of coactivator overexpression on AR transactivation.
  • Investigating the molecular basis of AR activation by coactivators.

Main Results:

  • A majority of recurrent prostate cancers exhibit high levels of AR.
  • High expression of coactivators, transcriptional intermediary factor 2 (TIF2) and steroid receptor coactivator 1 (SRC1), was observed in recurrent tumors.
  • Coactivator overexpression potentiates AR transactivation at physiological adrenal androgen levels.

Conclusions:

  • The androgen receptor (AR) and specific coactivators play a significant role in recurrent prostate cancer.
  • Overexpression of TIF2 and SRC1 provides a molecular mechanism for AR reactivation in recurrent prostate cancer.
  • These findings suggest a general mechanism for prostate cancer recurrence after ADT.

More Related Videos

Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients12:13

Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients

Published on: November 19, 2019

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...
GPCR Desensitization01:12

GPCR Desensitization

G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
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...
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include: