Related Experiment Video
Updated: Aug 16, 2026
Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer
Published on: April 13, 2015
The proapoptotic tumor suppressor protein kinase C-delta is lost in human squamous cell carcinomas
A M D'Costa1, J K Robinson, T Maududi
1Cardinal Bernardin Cancer Center, Skin Cancer Research Program, Loyola University Medical Center, Maywood, IL 60153, USA.
Abstract:
Protein kinase C (PKC)-delta is proapoptotic in human keratinocytes, and is downregulated or inactivated in keratinocytes expressing the activated Ha-ras oncogene, making it a candidate tumor suppressor gene for squamous cell carcinoma (SCC). We evaluated the significance of PKC-delta loss in transformed human keratinocytes using tumorigenic HaCaT Ras II-4 cells that have significantly reduced PKC-delta levels. Re-expression of PKC-delta by retrovirus transduction caused an increase in apoptosis and growth inhibition in culture. The growth inhibition induced by PKC-delta could be partially reversed by Bcl-x(L) expression, indicating that apoptosis was in part responsible for PKC-delta-induced growth inhibition. PKC-delta re-expression suppressed the tumorigenicity of HaCaT Ras II-4 cells in nude mice (P<0.05), and the small tumors that did form contained elevated levels of activated caspase-3, indicating increased apoptosis. In addition, we found that 29% (12/42) of human Bowen's disease (squamous carcinoma in situ) or SCC cases had absent or reduced PKC-delta when compared to the surrounding normal epidermis. These results indicate that PKC-delta inhibits transformed keratinocyte growth by inducing apoptosis, and that PKC-delta may function as a tumor suppressor in human SCCs where its loss in cells harboring activated ras could provide a growth advantage by conferring resistance to apoptosis.
Insights
Protein kinase C (PKC)-delta suppresses tumor growth by inducing apoptosis in keratinocytes. Loss of PKC-delta is linked to squamous cell carcinoma (SCC), suggesting its role as a tumor suppressor.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Protein kinase C (PKC)-delta is a proapoptotic factor in human keratinocytes.
- PKC-delta is downregulated in keratinocytes with activated Ha-ras oncogene, implicating it in squamous cell carcinoma (SCC) development.
- Loss of PKC-delta may confer a growth advantage to transformed keratinocytes.
Purpose of the Study:
- To evaluate the significance of PKC-delta loss in transformed human keratinocytes.
- To investigate the role of PKC-delta in SCC tumorigenesis.
- To determine if PKC-delta functions as a tumor suppressor in SCC.
Main Methods:
- Utilized tumorigenic HaCaT Ras II-4 cells with reduced PKC-delta levels.
- Re-expressed PKC-delta via retrovirus transduction.
- Assessed apoptosis, growth inhibition, and tumorigenicity in nude mice.
- Analyzed PKC-delta expression in human Bowen's disease and SCC samples.
Main Results:
- Re-expression of PKC-delta increased apoptosis and inhibited growth in HaCaT Ras II-4 cells.
- PKC-delta-induced growth inhibition was partially reversed by Bcl-x(L), confirming apoptosis's role.
- PKC-delta re-expression suppressed tumor formation in nude mice, with tumors showing increased caspase-3 activity.
- 29% of human SCC/Bowen's disease cases exhibited absent or reduced PKC-delta compared to normal epidermis.
Conclusions:
- PKC-delta inhibits transformed keratinocyte growth by inducing apoptosis.
- Loss of PKC-delta may contribute to SCC development by conferring resistance to apoptosis.
- PKC-delta functions as a tumor suppressor in human SCCs.
Related Concept Videos
01:12Loss of Tumor Suppressor Gene Functions
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...
01:12Loss of Tumor Suppressor Gene Functions
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...
02:23Abnormal Proliferation
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
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...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
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...
01:20The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...