The role of the genetp53isoforms in the human cancer and their outcome

Introduction. The p53 functions are ubiquitously altered in cancer cells by mutations/perturbation of it signaling path- ways, and loss of p53 activity is a prerequisite for cancer development. Mutant p53 is thought to play a pivotal role in promoting invasion, favoring cancer cell exit from the primary tumor site and dissemination, ultimately leading to metastasis formation [1].

Methods and materials. To study the effect of the TP53 gene on development tumor cells conducted a literature review and created scheme and illustrations.

Result. The molecular mechanisms of the decision making are still no well described. Indeed, in clinical studies, it has been difficult to link p53 mutation status to therapeutic response and clinical outcome, suggesting that additional factors may affect the p53 pathway. Despite 30 years of research on p53 demonstrating the key role of p53 in cancer treatment and prevention of cancer formation, it is still difficult in clinical studies to link p53 mutation status to cancer prognosis and cancer treatment. The whether p53δ mRNA leads to p53δ protein expression and whether p53δ has oncogenic activities. We have recently reported the analysis of p53β and p53γ mRNA expression in relation to clinical outcome and clinical markers in a cohort of 127 primary breast tumors. We determined that p53β and p53γ are not randomly expressed in breast cancer. Indeed, p53β is associated with p53γ expression, and p53γ is associated with p53 gene mutation, while p53β is associated with estrogen receptor expression (ER)[2].Interestingly, mutant p53 breast cancer patients expressing the p53γ isoform have low cancer recurrence and an overall survival as good as wild-type p53 breast cancer patients, independent of ER status. Conversely, mutant p53 breast cancer patients devoid of p53γ expression have a particularly poor prognosis. We did not observe any significant difference in wild-type p53 breast cancer patients whether they expressed p53β/ p53γ or not. Therefore, the determination of p53γ expression allows the identification of 2 populations of mutant p53 breast cancer patients with different prognoses, independent of ER status and cancer treatment. Indeed, mutant p53breast cancer patients expressing p53γ have a prog- nosis as good as wild-type p53 breast cancer patients, suggesting that they may respond better to treatment. On the other hand, mutant p53 breast cancer patients not expressing p53γ have a particularly poor prognosis probably because they poorly respond to treatment. p53γ isoform may provide an explanation of the hitherto inconsistent relationship between p53 mutation, treatment response, and outcome in breast cancer. [3,4]

Conclusion. In conclusion, the above clinical data report the expression of p53 isoforms in several types of cancer, confirming that p53 isoforms are expressed both at the mRNA and protein levels. Because p53 isoforms can regulate cell proliferation (cell cycle progression, senescence, and apoptosis) and are abnormally expressed in different cancer types, it suggests that their differential expression may disrupt the p53 response and contribute to tumor formation. Therefore, p53 isoforms may provide an explanation to the difficulties in many clinical studies to link p53 status to cancer prognosis and treatment. In cancer cells, restoration of p53β/p53γ or abolition of Δ133p53 expression would impair tumor cell growth by inducing senescence or cell death and therefore may represent novel therapeutic targets.



  1. Gadea, G., de Toledo, M., Anguille, C., and Roux, P. (2007). Loss of p53 promotes RhoA-ROCK- dependent cell migration and invasion in 3D matrices. J. Cell Biol. 178, 23–30.
  2. Bourdon J. P53 Isoforms Change P53 Paradigm. Mol Cell Oncol. 2014;1(4):e969136.
  3. Khoury MP, Bourdon J-C. p53 Isoforms: An Intracellular Microprocessor? Genes Cancer. 2011;2(4):453–65.
  4. Bourdon J. P53 Isoforms Change P53 Paradigm. Mol Cell Oncol. 2014;1(4):e969136.
Year: 2018
City: Shymkent
Category: Medicine