Related Experiment Video

Updated: Mar 1, 2026

In Vivo Augmentation of Gut-Homing Regulatory T Cell Induction
08:02

In Vivo Augmentation of Gut-Homing Regulatory T Cell Induction

Published on: January 22, 2020

6.0K

Vitamin D receptor activation reduces VCaP xenograft tumor growth and counteracts ERG activity despite induction of

Justin M Roberts1, Rebeca San Martin1, D Badrajee Piyarathna1,2

  • 1Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.

Oncotarget
|June 8, 2017
PubMed

Insights

A novel vitamin D receptor (VDR) agonist, VDRM2, effectively reduces prostate cancer growth without causing hypercalcemia. This VDR agonist shows promise for treating TMPRSS2:ERG positive prostate cancers.

Area of Science:

  • Oncology
  • Endocrinology
  • Molecular Biology

Background:

  • The role of vitamin D in prostate cancer prevention and therapy remains unclear.
  • Prostate cancers often express the TMPRSS2:ERG fusion gene, influenced by androgens and VDR activation.
  • Clinical use of VDR agonists is limited by hypercalcemia and CYP24A1 induction, which reduces VDR activity.

Purpose of the Study:

  • To investigate the therapeutic potential of a novel CYP24A1-resistant VDR agonist (VDRM2) in TMPRSS2:ERG positive prostate cancer.
  • To evaluate the impact of VDR activation on ERG activity and associated gene expression pathways.
  • To determine if VDRM2 can overcome limitations associated with conventional VDR agonists.

Main Methods:

  • Utilized the VCaP cell line, a model for TMPRSS2:ERG positive prostate cancer.
  • Administered a nonsecosteroidal, CYP24A1-resistant VDR agonist (VDRM2) to xenograft tumors.
  • Employed next-generation RNA sequencing and Gene Set Enrichment Analysis (GSEA) to analyze gene expression and ERG pathway activity.

Main Results:

  • VDRM2 significantly reduced xenograft tumor growth without inducing hypercalcemia.
  • RNA sequencing revealed substantial overlap in gene regulation between 1,25D(OH)2D3 and VDRM2.
  • VDR activation did not increase ERG activity and opposed key ERG-regulated gene pathways.

Conclusions:

  • A CYP24A1-resistant VDR agonist like VDRM2 may offer a beneficial therapeutic strategy for TMPRSS2:ERG positive prostate cancer.
  • VDR activation can counteract detrimental effects of ERG expression in prostate cancer.
  • Overcoming VDR inactivation caused by TMPRSS2:ERG is a potential therapeutic avenue.
Keywords:
CYP24A1TMPRSS2:ERGVCaPprostate cancervitamin D

More Related Videos

Experimental Melanoma Immunotherapy Model Using Tumor Vaccination with a Hematopoietic Cytokine09:15

Experimental Melanoma Immunotherapy Model Using Tumor Vaccination with a Hematopoietic Cytokine

Published on: February 24, 2023

4.1K
Ex vivo Expansion of Tumor-reactive T Cells by Means of Bryostatin 1/Ionomycin and the Common Gamma Chain Cytokines Formulation07:20

Ex vivo Expansion of Tumor-reactive T Cells by Means of Bryostatin 1/Ionomycin and the Common Gamma Chain Cytokines Formulation

Published on: January 14, 2011

15.3K

Related Concept Videos

Tumor Immunotherapy01:27

Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
2.1K
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
2.9K
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...
8.2K
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...
4.9K
Cancer Vaccines01:30

Cancer Vaccines

Cancer treatment vaccines are a rapidly evolving field that offers a promising approach to immunotherapy. Unlike traditional vaccines that prevent diseases, cancer treatment vaccines are designed to treat existing cancers by stimulating the immune system to recognize and attack cancer cells.
Cancer vaccines come in two categories: preventive (prophylactic) and treatment (active). Preventive vaccines, such as the Human Papillomavirus (HPV) vaccine, protect against viruses that cause certain...
1.2K
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
10.7K