These results suggest that RACK1 promotes cell growth and invasion and inhibits the senescence and apoptosis in cervical cancer cells probably by affecting the p53 pathway.
The inactivation of the wild-type p53 function resulting from a missense mutation, or the lack of detectable wild-type p53 protein due to the translational/post-translational deregulation of p53 protein levels may be the contributing factor in the tumorigenicity of these five cases of cervical cancer.
Thus, polymorphism of the p53 itself as well as in combination with HPV infection may not be a genetic risk for cervical cancer and therefore much attention should be paid to other risk factors such as sexual behavior and smoking.
Storey et al.(1998) implicated the proline/argine polymorphism of the codon 72 of the tumor-suppressor gene p53 in the development of cervical cancer (CC) with the observation that the p53 protein is more efficiently inactivated by the E6 oncoprotein of human papillomavirus in p53 arginine as compared with its proline isoform.
CP-31398, a styrylquinazoline, emerges from a screen for therapeutic agents that restore the wild-type DNA-binding conformation of mutant p53 to suppress tumors in vivo, but its effects on cervical cancer (CC) remain unknown.
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.
Constant expression of E6 and E7 mRNA by high-risk human papillomaviruses (HPV) abrogates p53 and retinoblastoma protein function, respectively, and is essential for the development of cervical cancer.
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.
Thus, our investigation of a larger set of clinical samples does not support the proposed association of any polymorphic status of p53 at codon 72 with an elevated risk for cervical cancer.
The purpose of this study was to analyze the association of 29 candidate single nucleotide polymorphisms (SNPs) in genes in the DNA repair pathway, TP53, and TP53BP1 with the risk of cervical cancer.
The expression of p53was negative in normal cervix, while there were 48 p53-positive cases (61.54%) and 30 p53-negative cases (38.46%) in patients with cervical cancer (p<0.05).
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.
These results indicate that transfection of cervical cancer cells with the wild-type p53 gene via Ad5CMV-p53 is a potential novel approach to the therapy of cervical cancer.
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.
We examined host p53 codon 72 genotype frequencies and found that patients with cervical abnormalities and women with HPV16 and HPV18 infections had a lower genotype frequency of the homozygous (AA) previously reported to be associated with cervical cancer, than uninfected women with no abnormalities.
The purpose of this study was to determine whether activation of the p53 and retinoblastoma (Rb) pathway by HPV-16 E6 and E7 repression was responsible for apoptosis and senescence of cervical cancer cells and to explore the potential of an antisense RNA (AS) transcript for gene therapy of cervical cancer.
Here, we report that downregulation of E6-AP expression by RNA interference results in both the accumulation of p53 and growth suppression of the HPV-positive cervical cancer cell lines HeLa and SiHa.
The objective was to evaluate the role of human papillomavirus (HPV) in the pathogenesis of papillary squamous cell carcinoma (PSCC) of the cervix and to determine cell proliferative activity and p53 abnormalities in these rare variants of cervical cancer.