Related Experiment Video

Updated: Aug 6, 2026

Establishment of a Clinic-based Biorepository
07:50

Establishment of a Clinic-based Biorepository

Published on: May 29, 2017

Gleevec suppresses p63 expression in head and neck squamous cell carcinoma despite p63 activation by DNA-damaging

Weg M Ongkeko1, Yi An, Theresa S Chu

  • 1Division of Head and Neck Surgery, Department of Surgery, University of California-San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA. wongkeko@ucsd.edu

The Laryngoscope
|August 4, 2006
PubMed
Abstract

Insights

Gleevec reduces p63/DeltaNp63 expression in head and neck squamous cell carcinoma (HNSCC) by inhibiting c-Abl. This finding has implications for cancer treatment, suggesting Gleevec may suppress tumors with high TAp63.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • p63 is a key regulator in squamous cell carcinomas.
  • p63 protein levels are modulated by DNA-damaging agents in head and neck squamous cell carcinoma (HNSCC).
  • The role of Gleevec (imatinib) in regulating p63 stability in HNSCC is not fully understood.

Purpose of the Study:

  • To determine the effects of Gleevec on p63 expression in HNSCC cell lines.
  • To investigate Gleevec's role in p63 stabilization under DNA-damaging conditions.
  • To elucidate the mechanism by which Gleevec affects p63 levels, focusing on the c-Abl pathway.

Main Methods:

  • Immunohistochemistry to assess p63 expression in HNSCC tissues.
  • Annexin V staining to evaluate p63's effect on apoptosis.
  • Immunoblotting and immunofluorescence to analyze p63 and c-Abl protein levels and expression patterns in response to Gleevec and DNA damage.

Main Results:

  • Gleevec dose-dependently reduces p63/DeltaNp63 expression in HNSCC cells.
  • Gleevec overrides the induction of p63 by DNA-damaging agents.
  • c-Abl kinase activity positively regulates p63 protein stability, and Gleevec inhibits this interaction.

Conclusions:

  • Gleevec downregulates p63/DeltaNp63 in HNSCC under normal and DNA-damaging conditions by inhibiting c-Abl.
  • Gleevec's effect on p63 isoforms (TAp63 vs. DeltaNp63) has differential implications for tumor suppression.
  • Targeted therapies discriminating between p63 isoforms are needed for precise HNSCC treatment strategies.

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

RNAscope for In situ Detection of Transcriptionally Active Human Papillomavirus in Head and Neck Squamous Cell Carcinoma10:26

RNAscope for In situ Detection of Transcriptionally Active Human Papillomavirus in Head and Neck Squamous Cell Carcinoma

Published on: March 11, 2014

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 daughter...
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.
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...
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...
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...