Despite heightened research interest over the last four decades, a clear picture of how wild type HsP53 functions as the guardian against malignant transformation remains elusive.
These results suggest that loss of p53 function and activation of phosphatidylinositol 3-kinase-AKT signaling pathways played important pathogenic roles in malignant transformation of the present case.
MDM2 can mediate the degradation of tumor suppressor p53 through an autoregulatory feedback loop, in which MDM2 abolishes wild-type p53 function and accelerates malignant transformation.
Higher intensity of p53 stained keratinocytes, no matter their low number, could represent mutant and more stable form of p53 protein, and at the same time signal for monitoring of disease due to potential malignant transformation.
Malignant neoplasia was found more frequently in patients with p53+ (P = .0006, OR = 7.67 [2.30; 25.54]) and PTEN- (P = .0043; OR = 5.43 [1.77; 16.61]).Immunohistochemical analysis using p53 and PTEN as markers, either alone or concomitantly, can be useful to predict malignant transformation in cases of endometrial polyps.
Because aberrant phosphorylation of cellular proteins is a hallmark of malignant transformation, the expression of the phosphorylated epitope could be an ideal antigen to combat cancer without damaging normal tissues. p53 activates transcription factors to suppress tumors by upregulating growth arrest and apoptosis-related genes.
The MDM2 homolog MDMX oncoprotein is indispensable for inhibition of p53 during normal embryonic development and malignant transformation, yet how MDMX harnesses p53 functions is unclear.
Thus, increased expression of cyclin D1 and cyclin E may be involved in cell cycle progression in psoriatic epidermis, and pRb and p53 may play important roles in the prevention of malignant transformation under the hyperproliferative state in psoriasis.
In agreement with the permissive role of TP53 mutations to oncogenic events, this report strongly suggests that TP53 mutations may promote malignant transformation of proliferating trophoblastic cells.
Indeed, a large body of work has shown that dysregulation of p53 and its E3 ligase MDM2 by the ubiquitin-proteasome system (UPS) promotes carcinogenesis and malignant transformation.
The results of our study suggest that amarogentin promotes apoptosis of liver cancer cells by the upregulation of p53 and downregulation of human telomerase reverse transcriptase and prevents the malignant transformation of these cells.
In response to various cellular stresses, p53 is activated and inhibits malignant transformation through the transcriptional regulation of its target genes.
We also examined TP53 and MDM2 protein immunohistochemistry (IHC) to assess the involvement of these differences in malignant transformation and disease progression.
Our study suggests that: (1) polysomy 6 and p16 deletion may contribute to adenomatous change of IPMN; (2) polysomy 7, polysomy 18, p16 deletion, and p53 deletion play roles in malignant transformation of noninvasive IPMN; and (3) polysomy 7 and p53 deletion may be excellent diagnostic markers for invasive IPMN.
Understanding the function of p53 in stem cells and its role in maintaining the balance between differentiation and malignant transformation can help shed light on cancer initiation and propagation, and hopefully also on cancer prevention and therapy.
We demonstrated that Skp2 inactivation decreased H3K4me3 levels, along with a reduction of cell growth, cell migration and malignant transformation of Pten/Trp53 double null MEFs, and further restrained prostate tumorigenesis of Pten/Trp53 mutant mice.