Related Experiment Video

Updated: Feb 17, 2026

Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors
08:45

Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors

Published on: July 17, 2020

6.7K

PARP-1 cooperates with Ptc1 to suppress medulloblastoma and basal cell carcinoma

Mirella Tanori1, Mariateresa Mancuso, Emanuela Pasquali

  • 1Section of Toxicology and Biomedical Sciences, Biotechnologies, Agro-Industry and Health Protection Department, Ente per le Nuove Tecnologie, l'Energia e l'Ambiente (ENEA), Centro Ricerche Casaccia, 00123 Rome, Italy.

Carcinogenesis
|July 29, 2008
PubMed

Insights

Poly(ADP-ribose) polymerase-1 (PARP-1) deficiency accelerates tumor development in mice with mutations in the patched (Ptc1) gene, which regulates sonic hedgehog signaling. This suggests PARP-1 suppresses tumors linked to this pathway when exposed to environmental stress.

Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • The patched (Ptc1) protein negatively regulates sonic hedgehog signaling, crucial for development and implicated in cancers like medulloblastoma and basal cell carcinoma (BCC).
  • Poly(ADP-ribose) polymerase (PARP-1) is vital for DNA damage signaling and repair; PARP-1-null mice exhibit extreme sensitivity to radiation and genomic instability.

Purpose of the Study:

  • To investigate the interaction between PARP-1 and sonic hedgehog signaling in tumor development.
  • To determine if PARP-1 deficiency influences the onset and progression of medulloblastoma and basal cell carcinoma in the context of Ptc1 mutations and radiation exposure.

Main Methods:

  • Crossed PARP-1-null mice with Ptc1 heterozygous mice to create double-mutant animals.
  • Exposed mice to radiation and monitored for tumor development, genomic instability, DNA damage foci (gamma-H2AX), and apoptosis.

Main Results:

  • PARP-1 deletion accelerated medulloblastoma development in irradiated Ptc1(+/-) mice, indicating PARP-1 inactivation sensitizes cerebellar cells to radiation-induced tumorigenesis.
  • Increased gamma-H2AX foci formation and slower disappearance, along with elevated apoptosis in PARP-1-deficient granule cell progenitors post-irradiation.
  • Double-mutant mice showed a striking susceptibility to BCC, with over 50% developing multiple, invasive tumors by 30 weeks of age.

Conclusions:

  • PARP-1 functions to suppress sonic hedgehog pathway-associated tumors that arise following environmental stress.
  • Genetic evidence supports a role for PARP-1 in preventing the development of radiation-induced medulloblastoma and basal cell carcinoma in the context of Ptc1 mutations.

More Related Videos

Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells09:24

Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells

Published on: August 12, 2015

9.6K
Analysis of Cell Cycle Position in Mammalian Cells12:19

Analysis of Cell Cycle Position in Mammalian Cells

Published on: January 21, 2012

61.4K

Related Concept Videos

DNA Damage Can Stall the Cell Cycle02:36

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...
3.2K
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...
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.
38.6K
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

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.
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,...
4.8K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
7.4K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
4.9K