Poly(ADP-ribose) polymerase-1 plays a role in suppressing mammary tumourigenesis in mice.

The DNA strand break-binding molecule, poly(ADP-ribose) polymerase-1 (PARP-1), plays a role in DNA repair, chromosomal stability, transcription and cell death. Accumulating evidence suggests that dysfunction of PARP-1 contributes to tumorigenesis. Here, we report that PARP-1 deficiency causes mammary carcinoma formation in female mice, and that the introduction of Trp53 mutations accelerates the onset and shortens the latency of mammary tumorigenesis.

Aflatoxin-B exposure does not lead to p53 mutations but results in enhanced liver cancer of Hupki (human p53 knock-in) mice.

Hepatocellular carcinoma (HCC) is a common human malignancy that is often associated with risk factors such as aflatoxin-B1 (AFB1) exposure and Hepatitis-B virus infection in developing countries. There is a strong correlation between these risk factors and mutation of the tumor-suppressor gene p53 at codon 249. In vitro experiments have also shown that treatment of human liver cells with AFB1 results in p53 mutations.

Heterozygous Men1 mutant mice develop a range of endocrine tumors mimicking multiple endocrine neoplasia type 1.

Multiple endocrine neoplasia type 1 (MEN1) is a hereditary syndrome characterized by the occurrence of multiple endocrine tumors of the parathyroid, pancreas, and anterior pituitary in patients. To study tumorigenesis related to the MEN1 syndrome, we have generated Men1 knockout mice using the gene targeting approach. Heterozygous Men1 mutant mice developed the same range of major endocrine tumors as is seen in MEN1 patients, affecting the parathyroid, pancreatic islets, pituitary and adrenal glands, as well as the thyroid, and exhibiting multistage tumor progression with metastatic potential.

UV-induced DNA damage and mutations in Hupki (human p53 knock-in) mice recapitulate p53 hotspot alterations in sun-exposed human skin.

The major etiological agent contributing to human nonmelanoma skin cancer is sunlight. The p53 tumor suppressor gene is usually mutated in these tumors, and the mutations are "UV signature" single or tandem transitions at dipyrimidine sequences in the DNA-binding domain (DBD). Cells that harbor these characteristic mutations are already present in sun-exposed skin areas of healthy individuals, and small epidermal patches that are immunoreactive to anti-p53 antibody accrue as exposure increases.