What happens if p53 is mutated?
TP53 gene mutations change single amino acids in p53, which impair the protein’s function. Without functioning p53, cell proliferation is not regulated effectively and DNA damage can accumulate in cells. Such cells may continue to divide in an uncontrolled way, leading to tumor growth.
Why is p53 mutated in cancer cells?
In some cases, malignant cancer cells bearing p53 mutations display a chemo-resistant phenotype. In response to a variety of cellular stresses such as DNA damage, p53 is induced to accumulate in cell nucleus to exert its pro-apoptotic function.
How does the mutated p53 affect the cell cycle?
P53 mainly promotes cell cycle arrest, DNA repair and, if the damage is anbnormally wide, apoptosis. The function of p53 is to avoid DNA changes accumulation which can lead to cancerogenesis (4-6). Cell cycle arrest and senescence are mainly mediated by a p53 downstream effector named p21 (encoded by the gene WAF).
What types of mutations are most likely in the p53 gene?
The most frequent location of p53 mutations was exon 7 and missense mutation was the most common type of mutation.
What cancers is p53 associated with?
P53 mutations associated with breast, colorectal, liver, lung, and ovarian cancers. Environ Health Perspect.
How is p53 mutation treated?
Reactivating p53 with Drugs Another experimental cancer therapy in development involves “patching” mutated p53 genes in cells so they can function normally again. Doctors could potentially use this medicine to treat cancer and prevent it by repairing defective p53 genes before cells have the chance to become cancerous.
How is p53 mutation detected?
Methods used for the detection of P53 mutations are based either on genomic DNA or mRNA as a template (11,12,15). The most widely used methods are based on DNA sequencing. However, few studies exist that compare sequencing assays by using both RNA and DNA targets (18–22).
What happens when p53 is upregulated?
p53 upregulation was especially pronounced in neural cells and p53 inhibition reduced neuronal apoptosis. The mutants with upregulated p53 network had similar changes in several p53-dependent and independent molecular pathways.
How does p53 help in cell regulation?
P53 forms a homotetrameric transcription factor that is reported to directly regulate ~500 target genes, thereby controlling a broad range of cellular processes, including cell cycle arrest, cell senescence, DNA repair, metabolic adaptation and cell death.
How common is p53 mutation?
However, the high frequencies of most of the hotspot mutations in the TP53 gene in human cancers appear to be independent of the tissue specificity observed in cancers, indicating a less important role than the mutations initiated by environmental mutagens.
What can cause mutations in p53?
Additional carcinogens are suspected to induce mutations in TP53 in various tissues such as bladder, liver, and colon. Overall, early mutations in the TP53 gene caused by various carcinogens are a typical example of the possible involvement of mutant p53 in tumor initiation and in early stages of tumor development.
Does phospholipase D stabilize the mutant p53 in MDA-MB-231 cells?
The human breast cancer cell line MDA-MB-231, which has high levels of a mutant p53, has high levels of phospholipase D (PLD) activity, which provides a survival signal in these cells when deprived of serum growth factors. We report here that the mutant p53 in MDA-MB-231 cells is stabilized by the elevated PLD activity in these cells.
What is the MDA-MB-231 cell line used to model?
The MDA-MB-231 cell line (isolated at M D Anderson from a pleural effusion of a patient with invasive ductal carcinoma) is commonly used to model late-stage breast cancer. This cell line is ER, PR, and E-cadherin negative and expresses mutated p53. In microarray profiling, the MDA-MB-231 cell genome clusters with the basal subtype of breast cancer.
Is p53 the most commonly mutated gene in human cancer?
Abstract. p53 is the most commonly mutated gene in human cancer. Although the loss of tumor suppressor functions for p53 in tumorigenesis is well characterized, gain-of-function p53 mutations observed in most cancers are not as widely appreciated. The human breast cancer cell line MDA-MB-231, which has high levels of a mutant p53,
Is HP1α downregulated in MDA MB-231?
HP1α is believed to counteract tumor progression since it is known to be downregulated in the invasive TNBC cell lines MDA-MB-231 and HS578T when compared with the ER/PR positive MCF7 and T47D [99]. Moreover, HP1α overexpression reduces the in vitro invasive phenotype of MDA-MB-231 [100].