Related Experiment Video
Updated: Nov 20, 2025
![Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate DMBA-TPA](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F60445.jpg&w=3840&q=50)
Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate DMBA-TPA
Published on: December 19, 2019
Tristetraprolin expression by keratinocytes protects against skin carcinogenesis
Assiya Assabban1, Ingrid Dubois-Vedrenne1, Laurye Van Maele1
1Institute for Medical Immunology, ULB Center for Research in Immunology, and ULB Center for Cancer Research, Université Libre de Bruxelles, Gosselies, Belgium.
Abstract:
Cancer is caused primarily by genomic alterations resulting in deregulation of gene regulatory circuits in key growth, apoptosis, or DNA repair pathways. Multiple genes associated with the initiation and development of tumors are also regulated at the level of mRNA decay, through the recruitment of RNA-binding proteins to AU-rich elements (AREs) located in their 3'-untranslated regions. One of these ARE-binding proteins, tristetraprolin (TTP; encoded by Zfp36), is consistently dysregulated in many human malignancies. Herein, using regulated overexpression or conditional ablation in the context of cutaneous chemical carcinogenesis, we show that TTP represents a critical regulator of skin tumorigenesis. We provide evidence that TTP controlled both tumor-associated inflammation and key oncogenic pathways in neoplastic epidermal cells. We identify Areg as a direct target of TTP in keratinocytes and show that EGFR signaling potentially contributed to exacerbated tumor formation. Finally, single-cell RNA-Seq analysis indicated that ZFP36 was downregulated in human malignant keratinocytes. We conclude that TTP expression by epidermal cells played a major role in the control of skin tumorigenesis.
Insights
Tristetraprolin (TTP) is a critical regulator of skin tumorigenesis, controlling inflammation and oncogenic pathways. Its downregulation in malignant keratinocytes highlights its role in skin cancer development.
Area of Science:
- Oncology
- Molecular Biology
- Dermatology
Background:
- Cancer arises from genomic alterations disrupting gene regulatory circuits.
- mRNA decay, influenced by RNA-binding proteins and AU-rich elements (AREs), affects tumor-associated genes.
- Tristetraprolin (TTP), an ARE-binding protein, is frequently dysregulated in human cancers.
Purpose of the Study:
- To investigate the role of TTP in skin tumorigenesis.
- To elucidate TTP's mechanisms in regulating inflammation and oncogenic pathways in epidermal cells.
Main Methods:
- Regulated overexpression and conditional ablation of TTP in a mouse model of skin cancer.
- Identification of TTP target genes using molecular biology techniques.
- Analysis of epidermal growth factor receptor (EGFR) signaling.
- Single-cell RNA sequencing (scRNA-Seq) of human malignant keratinocytes.
Main Results:
- TTP acts as a critical regulator in skin tumor development.
- TTP influences both tumor-associated inflammation and oncogenic pathways in neoplastic epidermal cells.
- Areg identified as a direct TTP target, with EGFR signaling contributing to tumor progression.
- ZFP36 (gene encoding TTP) is downregulated in human malignant keratinocytes.
Conclusions:
- TTP expression in epidermal cells is crucial for controlling skin tumorigenesis.
- Dysregulation of TTP impacts key pathways involved in skin cancer.
- TTP represents a potential therapeutic target for skin malignancies.
Related Concept Videos
01:12Renewal of Skin Epidermal Stem Cells
01:30Skin Cancer
Basal Cell Carcinoma (BCC): BCC is the most common type of skin cancer, accounting for about 80% of cases. It typically develops in...
01:24Cells of the Epidermis
The cells in all these layers except the stratum basale are called keratinocytes, a type of cell that manufactures and stores the protein keratin. The keratinocytes in the stratum corneum are dead and regularly slough away, being replaced by cells from...
02:23Abnormal Proliferation
01:19Pigmentation
Melanin occurs in two primary forms: eumelanin that provides black and brown pigment and pheomelanin that provides red color. Dark-skinned individuals produce more melanin than those with pale...
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,...