A polymorphism at codon 72 of p53 results in translation to either arginine (p53Arg) or proline (p53Pro), and recent study showed that Caucasian women with arginine form of p53 are more susceptible to HPV-associated carcinoma of the cervix.
In the cervical cancer cell (HeLa) with endogenous high TRIM3 expression, increased expression of miR-454-3p obviously inhibited TRIM3 expression and then manipulating cell growth and apoptosis, down-regulating the expression of P53 and cleaved caspase-3 via P38 MAPK signaling.
The E6AP ubiquitin-protein ligase (E3) mediates the human papillomavirus-induced degradation of the p53 tumor suppressor in cervical cancer and is mutated in Angelman syndrome, a neurological disorder.
The p21 arginine allele was significantly associated with CaCx in the p53 proline non-homozygous group of subjects (OR(age-adjusted) = 2.68; 95% CI: 1.21-5.91; P = 0.01), and specifically in the p53 heterozygous group (OR(age-adjusted) = 2.91; 95% CI = 1.12-7.56; P = 0.03).
Thus, these findings suggested that uc.206 acts as a novel oncogene by targeting the P53 gene and promoting CC cell growth, which might be beneficial for cervical cancer therapy.
Our study explored whether p53 status, human papilloma virus (HPV), and LOH on chromosome 3p21.3, 6p21.2, 17p13.1, and 18q21.2 are associated with treatment outcome in 65 patients with cervical cancer after radiotherapy.
It may be assumed that the low incidence of cervical cancer in Israeli Jewish women and the differences between the ethnic groups may be related to the frequency pattern of the homozygous arginine p53 polymorphism
Cervical carcinoma is associated with certain types of human papillomaviruses expressing the E6 and E7 oncogenes, which are involved in carcinogenesis through their interactions with the p53 and pRB pathways, respectively.
hMSH2 immunoreactivity was correlated with p53 and weakly correlated with apoptosis. hMSH2 immunoreactivity could not be correlated to any tumour markers, while apoptosis correlated significantly with T stage, FIGO classification and the relative risk of death from cervical cancer.
These data suggest that there are significant associations between the miR-502-binding site SNP in the 3'-UTR of SET8 and the TP53 codon 72 polymorphism with cervical cancer in Chinese, and there is a gene-gene interaction.
Recently, it has been demonstrated that the presence of homozygous arginine at codon 72 renders p53 about seven times more susceptible to E6-mediated proteolytic degradation as well as to cervical cancer than those with proline homozygotes or proline/arginine heterozygotes.
To confirm this result we examined the proportion of p53 genotypes in a larger number of patients with cervical cancer and in patients with squamous intraepithelial lesions (SIL) compared to a control population.
Accordingly, these data demonstrate that the anticancer activity of B1 is associated with the activation of p53 and the release of cytochrome c, which suggest that B1 might have therapeutic potential against cervix carcinoma as an effective lead compound.
Human papilloma virus (HPV) infection is the most important risk factor for cervical cancer development. p53 based gene therapy is not suitable for cervical cancer because HPV oncoprotein E6 inactivates p53 protein by targeting it for ubiquitin mediated degradation.