Related Experiment Video

Updated: Jul 3, 2026

Cell Population Analyses During Skin Carcinogenesis
06:53

Cell Population Analyses During Skin Carcinogenesis

Published on: August 21, 2013

Heterozygous mutations in the tumor suppressor gene PATCHED provoke basal cell carcinoma-like features in human

F Brellier1, V Bergoglio, A Valin

  • 1Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.

Oncogene
|August 6, 2008
PubMed

Insights

Heterozygous PATCHED mutations in skin cells promote invasiveness and hyperproliferation, contributing to basal cell carcinoma development. This suggests a haploinsufficiency mechanism in cancer proneness.

Area of Science:

  • Oncology
  • Dermatology
  • Molecular Biology

Background:

  • Basal cell carcinoma (BCC) is the most common human cancer.
  • Most BCCs show aberrant activation of the SONIC HEDGEHOG (SHH)/PATCHED pathway.
  • Mutations in the PATCHED tumor suppressor gene are key triggers.

Purpose of the Study:

  • To investigate the role of heterozygous PATCHED mutations in BCC development.
  • To model early somatic mutations in the PATCHED gene using patient-derived keratinocytes.
  • To understand the physiological impact of haploinsufficiency in skin cancer.

Main Methods:

  • Utilized healthy keratinocytes from Gorlin syndrome patients (PATCHED(+/-) genotype).
  • Developed PATCHED(+/-) epidermis on a dermal equivalent with wild-type fibroblasts.
  • Analyzed keratinocyte phenotype, including proliferation, differentiation, and gene expression.

Main Results:

  • PATCHED(+/-) epidermis showed increased invasiveness, hyperproliferation, and impaired differentiation.
  • Keratinocytes exhibited elevated levels of transcriptional activators GLI1 and GLI2.
  • A significant increase in the cell cycle regulator cyclin D1 was observed.

Conclusions:

  • Constitutive heterozygous PATCHED mutations have a significant physiological impact on primary human keratinocytes.
  • These findings support a haploinsufficiency mechanism in cancer proneness for BCC.
  • The study provides novel insights into the early stages of basal cell carcinoma development.

More Related Videos

Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate (DMBA-TPA)04:12

Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate (DMBA-TPA)

Published on: December 19, 2019

3D Organotypic Co-culture Model Supporting Medullary Thymic Epithelial Cell Proliferation, Differentiation and Promiscuous Gene Expression06:47

3D Organotypic Co-culture Model Supporting Medullary Thymic Epithelial Cell Proliferation, Differentiation and Promiscuous Gene Expression

Published on: July 30, 2015

Related Concept Videos

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...
Skin Cancer01:30

Skin Cancer

Skin cancer is a type of cancer that occurs when there is an abnormal growth of skin cells, usually triggered by damage to the DNA within the skin cells. It is primarily caused by exposure to ultraviolet (UV) radiation from the sun or artificial sources like tanning beds. Skin cancer is the most common type of cancer worldwide, and its incidence continues to rise.
Basal Cell Carcinoma (BCC): BCC is the most common type of skin cancer, accounting for about 80% of cases. It typically develops in...
Cancers Originate from Somatic Mutations in a Single Cell02:21

Cancers Originate from Somatic Mutations in a Single Cell

Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
Cancers Originate from Somatic Mutations in a Single Cell02:21

Cancers Originate from Somatic Mutations in a Single Cell

Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
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...
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...