During cancer progression p53 undergoes mutation and following mutations it acts as an oncogene and its increased expression is associated with poor prognosis in several cancers including mammary tumours in humans as well as dogs.

p53 is involved in tumor suppression. Mutation in gene coding for p53 acts to inhibit barriers to cancer progression. Without mutation in the TP53 gene cellular barriers to prevent carcinogenesis is maintained.

p53 is transcription factor encoded by TP53 gene that acts to control the cell cycle via sensing genetic instability. DNA damage recognition initiates p53 mediated cell cycle arrest at the G2 check Point. p53 acts to initiate DNA repair allowing the cell to renter the cell cycle with maintained genetic integrity. Under extreme damage, p53 acts to initiate apoptosis in these cells where damage is beyond repair. Mutation in the TP53 gene gives cancerous cells immortal properties.

For carcinogenesis to proceed cancers must evade apoptosis and maintain genomic states of aneuploidy. For this to occur, p53 mediated machinery must be inhibited.

p53 is mutated in roughly 50 percent of cancers.

P53 is often mutated in solid malignancies. P53 function is like a guardian of the genome, activating apoptosis if it perceives DNA damage. For this reason p53 function is mostly nuclear. A number of p53 mutations in cancer cause p53 accumulation into the cytoplasm. Therefore, a cancer with a cytoplasmic p53 pattern of staining it is likely to carry p53 mutations. Noteworthy, there are other p53 mutations which completely abrogate p53 expression (p53 null). Thereby looking only at protein expression could be misleading to draw conclusions on the status of p53 (wild type vs. mutation).

Coming back to your question, this can explain why in some cases p53 accumulation is associated with "oncogene-like" behavior. Indeed, p53 in the cytoplasm will be "off-target" and mutations into the genome will be accumulated in a cancer cell without activation of p53 function. By the way, the notion that a cancer with p53 mutations will have a worst outcome should be taken case by case, since this is not always true. It will also depend on the kind of treatment and the cancer tissue.

Due to the impaired function of the mutated p53, some of the feedback mechanisms regulating p53 expression are not operational; i.e. accumulation of p53 is often regarded as a surrogate marker for non-functional p53.

Our research showed that was a significant inverse correlation between p53 overexpression and response to chemotherapy and a stronger association between high P53 overexpression (%) and a genetic mutation of p53 (p=0.0001). More than 50% overexpression indicated a strong probability of genetic mutation. There was no association between response to chemotherapy and age-groups or TNM classification (p=0.2), but there was a significant one between sex and site of tumour (p

Dear Kuldipa

All answers are correct, in more than 60% of tumors, the p53 expresses but without any effective function, may be with follow reasons:

- Mutation in hot point

- The promoter of MDM2 (or HDM2 as one of p53 target genes ) show more responsible to p53. More p53, more MDM2 transcription

- P53 more sensitive to E6 follow activation of MDM2

- P53 failed to translocate in nuclear

Good Luck

Yes, p53 is a tumor suppressor gene. Agree with Jose's post.

as to why more p53 in various cancers is associated with more aggressive phenotypes? We (pathologists) believe that what we see (by immunohistochemistry) is an accumulation of mutant and therefore non-functional p53 in the nucleus, while wild type p53 should not be accumulating to the same degree. I have to point out though that this is a hypothesis and I am not aware of the experimental proof. The same phenomenon is p16 accumulation in more advanced cervical dysplasia and cancer - although this is a tumor suppressor gene.

Article Prediction of risk scores for colorectal cancer patients fro...