Efficient growth inhibition of HPV 16 E6-expressing cells by an adenovirus-expressing p53 homologue p73beta

Related Experiment Video

Updated: Aug 12, 2026

Use of Interferon-γ Enzyme-linked Immunospot Assay to Characterize Novel T-cell Epitopes of Human Papillomavirus
13:41

Use of Interferon-γ Enzyme-linked Immunospot Assay to Characterize Novel T-cell Epitopes of Human Papillomavirus

Published on: March 8, 2012

Sanjeev Das1, Wafik S El-Deiry, Kumaravel Somasundaram

  • 1Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560 012, India.

Oncogene
|November 25, 2003
PubMed

Insights

A novel gene therapy using adenovirus expressing p73beta (Ad-p73) effectively inhibits cervical cancer cell growth. This approach targets human papillomavirus (HPV) E6-expressing cells, offering a potential treatment for cervical cancer.

Area of Science:

  • Oncology
  • Gene Therapy
  • Molecular Biology

Background:

  • Tumor suppressor p53 is inactivated by human papillomavirus (HPV) E6 oncoprotein in cervical cancers.
  • p73, a p53 homologue, is resistant to HPV E6-mediated degradation.
  • This resistance presents an opportunity for therapeutic intervention.

Purpose of the Study:

  • To develop and evaluate a replication-deficient recombinant adenovirus expressing p73beta (Ad-p73) as a potential gene therapy for cervical cancer.
  • To assess the efficacy of Ad-p73 in inhibiting the growth of cancer cells, particularly those expressing HPV E6.
  • To investigate the mechanism of Ad-p73 action, including its effect on cell cycle and apoptosis.

Main Methods:

  • Development of a replication-deficient recombinant adenovirus expressing p73beta (Ad-p73).
  • Infection of human cancer cells, including HPV E6-expressing cell lines and HeLa cells, with Ad-p73.
  • Analysis of p73beta and its target gene p21(WAF1/CIP1) expression levels.
  • Assessment of cellular DNA synthesis, cell cycle progression (G1 arrest), apoptosis, and cell growth inhibition.

Main Results:

  • Ad-p73 infection significantly increased p73beta and p21(WAF1/CIP1) levels in cancer cells.
  • Ad-p73 induced G1 cell cycle arrest, reduced DNA synthesis, and promoted apoptosis.
  • Ad-p73 demonstrated potent inhibition of cancer cell growth, outperforming Ad-p53 in HPV E6-expressing cells.
  • HeLa cells, a cervical cancer cell line, were efficiently growth-inhibited by Ad-p73.

Conclusions:

  • Ad-p73 effectively inhibits the growth of cervical cancer cells, including those expressing HPV E6.
  • The stable expression of functional p73 in the presence of E6 is crucial for Ad-p73's therapeutic effect.
  • Ad-p73 represents a promising gene therapy candidate for cervical cancer treatment.

More Related Videos

Yeast As a Chassis for Developing Functional Assays to Study Human P5314:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

Identifying Inhibitors of the HBx-DDB1 Interaction Using a Split Luciferase Assay System05:55

Identifying Inhibitors of the HBx-DDB1 Interaction Using a Split Luciferase Assay System

Published on: December 21, 2019

Related Concept Videos

Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
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...