Related Experiment Video

Updated: Oct 11, 2026

Preparation of Cell-lines for Conditional Knockdown of Gene Expression and Measurement of the Knockdown Effects on E4orf4-Induced Cell Death
13:54

Preparation of Cell-lines for Conditional Knockdown of Gene Expression and Measurement of the Knockdown Effects on E4orf4-Induced Cell Death

Published on: October 21, 2012

Adenovirus E1A oncogene expression in tumor cells enhances killing by TNF-related apoptosis-inducing ligand (TRAIL)

J M Routes1, S Ryan, A Clase

  • 1Department of Medicine and Immunology, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206, USA. routesj@njc.org

Journal of Immunology (Baltimore, Md. : 1950)
|October 18, 2000
PubMed

Insights

Adenovirus type 5 E1A oncogene expression sensitizes cells to TRAIL-induced apoptosis. However, other viral gene products, specifically E3 and E1B-19K, inhibit this TRAIL sensitivity.

Area of Science:

  • Oncology
  • Virology
  • Molecular Biology

Background:

  • The adenovirus type 5 (Ad5) E1A oncogene is known to sensitize cells to apoptosis induced by TNF-alpha and Fas-ligand.
  • Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mediates cell death through a similar pathway, prompting investigation into E1A's effect on TRAIL sensitivity.

Purpose of the Study:

  • To determine if adenovirus type 5 (Ad5) E1A oncogene expression sensitizes human cancer cells to TRAIL-induced apoptosis.
  • To investigate the role of other Ad5 gene products (E1B and E3) in modulating TRAIL sensitivity.

Main Methods:

  • Human melanoma (A2058) and fibrosarcoma (H4) cells were engineered to express Ad5 E1A via stable transfection or Ad5 infection.
  • Cells were subsequently exposed to TRAIL to assess apoptosis and cell lysis.
  • Experiments utilized Ad5 mutants lacking E3 (H5dl327) or E1B-19K (H5dl250) coding regions to evaluate their impact on TRAIL sensitivity.

Main Results:

  • Stable expression of Ad5 E1A in A2058 and H4 cells significantly increased their sensitivity to TRAIL-induced killing.
  • Conversely, Ad5 infection, even at high E1A levels, rendered cells resistant to TRAIL, indicating inhibition by other viral products.
  • Ad5 E3 gene products were found to strongly inhibit TRAIL-induced killing, while E1B-19K showed a lesser inhibitory effect.

Conclusions:

  • Ad5 E1A expression confers sensitivity to TRAIL-mediated apoptosis in cancer cells.
  • Ad5 viral gene products, particularly E3 and E1B-19K, counteract the sensitizing effect of E1A, inhibiting TRAIL-induced cell death.

More Related Videos

Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo12:42

Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo

Published on: January 7, 2019

Genome-wide RNAi Screening to Identify Host Factors That Modulate Oncolytic Virus Therapy08:51

Genome-wide RNAi Screening to Identify Host Factors That Modulate Oncolytic Virus Therapy

Published on: April 3, 2018

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.
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
Cytotoxic T Cells-mediated Immune Response01:27

Cytotoxic T Cells-mediated Immune Response

Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
Rous Sarcoma Virus (RSV) and Cancer01:03

Rous Sarcoma Virus (RSV) and Cancer

Rous Sarcoma virus or RSV was discovered by F. Peyton Rous in the year 1911 as a filterable transmissible agent that could cause tumors in chickens. He won a Nobel Prize for this discovery in 1966. His experiments clearly demonstrated that some cancers could be caused by infectious agents and led to the discovery of many more cancer-causing viruses in animals as well as humans.
RSV is a retrovirus that contains two copies of a plus-strand  RNA genome. Its genome consists of four main open...
Enzyme-linked Receptors01:13

Enzyme-linked Receptors

Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
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...