Related Experiment Video

Updated: Nov 25, 2025

Generation of Integration-free Human Induced Pluripotent Stem Cells Using Hair-derived Keratinocytes
08:36

Generation of Integration-free Human Induced Pluripotent Stem Cells Using Hair-derived Keratinocytes

Published on: August 20, 2015

11.9K

HPV-inactive cell populations arise from HPV16-transformed human keratinocytes after p53 knockout

Fadi Abboodi1, Phillip Buckhaults2, Diego Altomare2

  • 1Department of Pathology, Microbiology, & Immunology, School of Medicine, University of South Carolina, USA; Department of Drug Discovery and Biomedical Sciences, College of Pharmacy, University of South Carolina, USA; Department of Pediatrics, Mosul Medical College, University of Mosul, Iraq.

Virology
|December 15, 2020
PubMed

Insights

Loss of p53 function in human papillomavirus (HPV) 16-infected cells reduces viral oncogene E7 expression and dependence on HPV. This suggests p53 loss may initiate HPV-inactive cancers.

Area of Science:

  • Oncology
  • Virology
  • Molecular Biology

Background:

  • Human papillomavirus (HPV)-inactive cancers possess HPV DNA but lack viral oncoprotein expression.
  • HPV-positive tumors can develop inactive metastases, suggesting a loss of viral oncogene dependence during cancer progression.

Purpose of the Study:

  • To investigate the role of p53 loss in the development of HPV-inactive cancers.
  • To test the hypothesis that HPV-inactive cancers originate from active lesions that lose E6/E7 dependence.

Main Methods:

  • CRISPR-Cas9 was used to create p53 knockout (p53-KO) in HPV16-immortalized human keratinocytes (HKc/DR).
  • Quantitative analysis of E7 mRNA levels and in-situ hybridization were performed.
  • The effect of 5-Aza-2 deoxycytidine on E7 expression in p53-KO cells was assessed.

Main Results:

  • p53 knockout led to a significant reduction in HPV16 E7 mRNA levels.
  • DNA methylation inhibition restored E7 expression in p53-KO cells.
  • p53-KO cell populations showed a mix of E6/E7-positive and negative cells.

Conclusions:

  • Loss of p53 function predisposes HPV16-transformed cells to downregulate viral oncogene expression.
  • This downregulation suggests a mechanism for the genesis of HPV-inactive cancers, where cells become independent of continuous HPV oncogene activity.
Keywords:
CRISPR-Cas9Cervical cancerHPV inactive CancerHPV16Head and neck cancerHuman papillomavirusSIX1p53

More Related Videos

Establishment of Proliferative Tetraploid Cells from Nontransformed Human Fibroblasts10:04

Establishment of Proliferative Tetraploid Cells from Nontransformed Human Fibroblasts

Published on: January 8, 2017

7.5K
Generation of Organotypic Raft Cultures from Primary Human Keratinocytes07:26

Generation of Organotypic Raft Cultures from Primary Human Keratinocytes

Published on: February 22, 2012

19.6K

Related Concept Videos

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...
4.9K
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
5.5K
DNA Damage can Stall the Cell Cycle02:37

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
9.7K
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...
5.3K
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.
37.5K