How does mutation in the p53 gene lead to cancer?

Cancer-Predisposing p53 Mutations

What is the p53 gene and how does it relate to cancer?

A gene that makes a protein that is found inside the nucleus of cells and plays a key role in controlling cell division and cell death. Mutations (changes) in the p53 gene may cause cancer cells to grow and spread in the body.

How does a mutated p53 gene encourage abnormal growth?

Mutated p53 genes are believed to be responsible for causing tumor growth because they turn off the regulatory mechanisms that keep cells from dividing out of control. Sometimes cells with negative regulators can halt their transmission by inducing pre-programmed cell death called apoptosis.

What cancer is p53 associated with?

P53 mutations associated with breast, colorectal, liver, lung, and ovarian cancers. Environ Health Perspect.

How often is p53 mutated in cancer?

The p53 gene contains homozygous mutations in ~50–60% of human cancers. About 90% of these mutations encode missense mutant proteins that span ~190 different codons localized in the DNA-binding domain of the gene and protein.

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Is p53 associated with hereditary cancers?

The majority of sporadic cancers exhibit loss of p53 activity due to mutations or deletions of TP53, and alterations in its signaling pathway. Germline TP53 mutations have been identified in a group of families exhibiting a rare but highly penetrant familial cancer syndrome, called the Li-Fraumeni syndrome (LFS).

How is p53 mutation treated?

Many researchers believe the emerging science of gene therapy holds the key. A gene therapy treatment based on restoring p53 could be safely combined with traditional cancer treatments such as surgery, chemotherapy or radiation therapy to increase the overall effectiveness of the treatment plan.

Is p53 good or bad?

p53, famously dubbed ‘The Guardian of the Genome’, is arguably the most significant gene for cancer suppression. Somatic loss of function of p53 underpins tumor progression in most epithelial cancers and many others besides.

What happens if both p53 alleles are mutated?

While carcinogenesis requires the loss of both alleles of most tumor suppressor genes, mutation of one allele of p53 can result in loss of function.

How is p53 inactivated?

In addition to genetic inactivation, the p53 protein can be functionally inactivated in cancer, through post-transductional modifications, changes in cellular compartmentalization, and interactions with other proteins.

What does p53 positive mean?

Marks et al. reported that p53 positivity was defined as a single malignant breast epithelial cell with positive nuclear staining for p53 (19). Martinazzi et al. reported that some nuclei with mutant p53 protein staining were considered positive (20).

What causes a cell to become cancerous?

Cancer is unchecked cell growth. Mutations in genes can cause cancer by accelerating cell division rates or inhibiting normal controls on the system, such as cell cycle arrest or programmed cell death. As a mass of cancerous cells grows, it can develop into a tumor.

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What is the role of tumor suppressor genes?

Tumor suppressor genes are normal genes that slow down cell division, repair DNA mistakes, or tell cells when to die (a process known as apoptosis or programmed cell death). When tumor suppressor genes don’t work properly, cells can grow out of control, which can lead to cancer.