Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Molecular biologic studies have shown that human papillomavirus (HPV), some oncogenes and tumor suppressor genes are associated with uterine cervical carcinogenesis. We examined HPV DNA typing and its gene expression, oncogenes (c-myc, EGF-R, c-erb B2) and p53 in cervical dysplasia and cancer with molecular biologic, immunohistochemical technique and binding assay to establish a gene diagnosis of uterine cervical cancer. The HPV study revealed that HPV DNA was detected at a high frequency at a higher grade of dysplasia and in the early stage of cervical cancer; especially HPV type 16 was associated with cervical carcinogenesis. In the oncogene study, c-myc gene overexpression was recognized in the advanced stage of cervical cancer. The other oncogene and p53 were found in a low frequency and were non-specific genes in cervical cancer. These findings indicated that HPV DNA diagnosis is a useful tool for screening the high risk group of cervical precancerous lesions and that oncogene detection might be useful in determining the biological behavior of a malignant tumor.
 ...
PMID:[Gene diagnosis of uterine cervical cancer]. 790 55

Endometrial cancers have been considered to be less prevalent in Japan than in Western countries. However, with the increase in life expectancy, the Westernization of the Japanese diet, and changes in the hormonal environment, the prevalence of the disease has gradually increased even in our country. Similar increases in cancers of the breasts, lungs, colons, and ovaries have been noted in recent years. Much is still unknown regarding the pathogenesis and natural history of endometrial cancer. Although endometrial hyperplasia is considered to be a precancerous lesion of endometrial carcinoma, the relationship between those diseases has not been elucidated to the same degree as that between cervical cancer and cervical dysplasia, or carcinoma in situ. Research findings in genetic oncology have revealed that tumorigenesis involves a multi-step process. It is probable that activation of multiple genes, inactivation of anti-oncogenes, and disappearance of normal inhibitor genes occur in the process of the development of endometrial cancer. The purpose of this study is to elucidate the relationship between oncogenes and the development of endometrial cancer. In addition, the significance of endometrial hyperplasia as a clinical entity is also be evaluated. The roles played by oncogenes in endometrial cancers and endometrial hyperplasias were examined using the most recent molecular biological and immunohistochemical methods. Also, the differences in cellular proliferation and tissue invasiveness were discussed. Results obtained were as follows. Evaluation of cell proliferation (PCNA, FCM) revealed that there was no difference in proliferative activity between atypical hyperplasia and well differentiated adenocarcinoma. Evaluation of oncogene abnormalities (c-myc,c-erbB-2,K-ras,p53) revealed that the development of endometrial cancer was a multistep process involving several oncogenes, as it has been noted in the development of other cancers. Evaluation of extracellular matrix and related factors (cathepsin D, laminin, type IV collagen, tenascin, CD44) showed that tissue invasiveness differed between atypical hyperplasia and well differentiated adenocarcinoma.
 ...
PMID:[Evaluation of the degree of biological behavior in endometrial hyperplasia and endometrial carcinoma: an investigation of proliferative activity, oncogene, and extracellular matrix]. 810 84

We investigated aberrant p53 expression in 81 cases of cervical intra-epithelial neoplasias (CIN) using a polyclonal antibody CM-1. The presence of human papillomavirus (HPV) DNA was evaluated by in situ and dot blot hybridization. Significant (more than 1% of cells positive) p53 positivity was found in three cases (4%) of which only one contained HPV DNA. In an additional nine cases, occasional p53 staining was found in basal epithelial cells, frequently associated with epithelial hyperplasia and increased subepithelial inflammation. The results show that aberrant p53 expression is an infrequent finding in CIN lesions. It can be seen in lesions both with and without HPV infection. Most importantly, there was no p53 expression in most cases of HPV-negative CIN, suggesting that p53 inactivation is not an obligatory step in the development of cervical dysplasia. However, our findings do not exclude the possibility that p53 mutations can occur later in the course of cervical carcinogenesis.
 ...
PMID:Aberrant p53 protein expression in cervical intra-epithelial neoplasia. 831 22

Cervical carcinomas and their precursors (cervical dysplasia, CIN1-3) are associated with human papillomavirus (HPV) infections. Epidemiological and in vitro-studies have shown that some of the genital HPV types, the high risk-types 16, 18, 31 etc., code for proteins (E6/E7) which strongly influence the cell cycle and genome stability. Progression from weak to severe dysplasia and to invasive cancer is associated with increasing expression of these viral oncogenes. Which additional cofactors contribute to progression of some dysplasias to carcinomas is still a matter of investigation. Recent results point to genetic predisposition (p53 polymorphism), cellular immune reaction, and cytokine expression. For HPV detection in cervical swabs and biopsies two highly sensitive and reliable systems (PCR, Hybrid Capture system) are available. Although classical histological methods are sufficient for the diagnosis of high-grade lesions and invasive cancer, HPV testing might give valuable diagnostic and prognostic clues especially in cases of unclear cytology (ASCUS) or weak dysplasia.
 ...
PMID:[Natural course of HPV infection. Usefulness of HPV analysis in cervix diagnosis]. 1009 Dec 28

Like other types of pre-malignant lesions and carcinoma, angiogenesis is associated with high-grade cervical dysplasia and with invasive squamous carcinoma of the cervix. Vascular endothelial cell growth factor (VEGF) is known to be one of the most important inducers of angiogenesis and is upregulated in carcinoma of the cervix. Human Papilloma Virus 16 (HPV-16) has been etiologically linked to human cervical cancer, and the major oncogenic proteins encoded by the viral genome, E6 and E7, are involved in the immortalization of target cells. Because several oncogenes including mutant ras, EGF receptor, ErbB2/Her2, c-myc and v-src upregulate VEGF expression, we asked whether HVP-16 E6 oncoprotein could act in a similar fashion. We found that HPV-16 E6-positive cells generally express high levels of VEGF message. Furthermore, co-expression of the VEGF promoter-Luc (luciferase) reporter gene with E6 in both human keratinocytes and mouse fibroblast showed that E6 oncoprotein upregulates VEGF promoter activity, and does so in a p53 independent manner. An E6 responsive region which comprises four Sp-1 sites, between -194 and -50 bp of the VEGF promoter, is also necessary for constitutive VEGF transcription. Taken together, our results suggest the possibility that the HPV oncoprotein E6 may contribute to tumor angiogenesis by direct stimulation of the VEGF gene.
 ...
PMID:Oncogenes and tumor angiogenesis: the HPV-16 E6 oncoprotein activates the vascular endothelial growth factor (VEGF) gene promoter in a p53 independent manner. 1103 Jan 50

The genomic alterations in preneoplastic lesions are summarized in this review. 3p and 9p in the lung, 9p in the bladder, 8p in the prostata, 19q and 1p in oligodendroglioma, and 22q in meningioma were reported to be deleted. Somatic mutation of p53 was found in preneoplastic lesions of the esophagus, stomach, colon, thyroid, and astrocytoma. Adenoma-carcinoma sequence (Apc, ras, p53 gene alterations) in colon, LKB1 gene in Peutz-Jeghers syndrome, Smad4 in juvenile polyposis, hMSH2, hMLH1, PMS1, PMS2 genes in HNPCC, VHL gene in kidney, WT1 in Wilms tumor, RB gene in retinoblastoma, and ret gene in MEN were reportedly altered in preneoplastic lesions involved in hereditary tumors. Cervical dysplasia and papilloma of the head and neck infected by human papilloma virus and liver infected by B-type hepatitis virus are also precancerous. Genomic instability, APC gene alteration, point mutation of K-ras in preneoplastic lesions of stomach and K-ras and p16 alterations in metaplasia of pancreas were also found. Advances in research on genomic alterations in preneoplastic lesions will contribute to prevention and early detection of cancer.
 ...
PMID:[Genomic alterations in preneoplastic lesions]. 1250 66

14-3-3 sigma (sigma) has been a major G2/M checkpoint control gene and has demonstrated that its inactivation in various cancers occurs mostly by epigenetic hypermethylation, not by genetic change. In order to confirm 14-3-3sigma protein expression together with p16 and p53 in cervical cancers, immunohistochemistry was performed using various histological subtypes of cervical cancers and dysplasia. Strong and diffuse immunoreactivity for 14-3-3sigma was uniformly observed in all the cervical dysplasia (17/17) and squamous cell carcinomas (29/29) including human papillomavirus (HPV)-negative cases. Even in adenosquamous carcinomas and adenocarcinomas of the cervix, immunohistochemical expression of 14-3-3sigma was shown with relatively high frequency (13/15, 87% and 22/27, 81%). In the in situ hybridization study, mRNA of 14-3-3sigma was expressed in six of eight immunohistochemical-negative cases. Therefore, the undetectable expression of 14-3-3sigma protein in cervical cancers might, at least in part, be due to a proteolysis not epigenetic hypermethylation. It is of interest that cancers without 14-3-3sigma expression were predominantly those lacking HPV DNA, and that there were no cases with concomitant inactivation of 14-3-3sigma and p16 in the present study. These observations are consistent with the hypothesis that inactivation of either 14-3-3sigma or p16 has an effect equivalent to the expression of E6 and E7 oncoproteins of HPV.
 ...
PMID:Immunohistochemical expression of 14-3-3 sigma protein in various histological subtypes of uterine cervical cancers. 1548 63

Histone deacetylases (HDACs) 1 and 2 share a high degree of homology and coexist within the same protein complexes. Despite their close association, each possesses unique functions. We show that the upregulation of HDAC2 in colorectal cancer occurred early at the polyp stage, was more robust and occurred more frequently than HDAC1. Similarly, while the expression of HDACs1 and 2 were increased in cervical dysplasia and invasive carcinoma, HDAC2 expression showed a clear demarcation of high-intensity staining at the transition region of dysplasia compared to HDAC1. Upon HDAC2 knockdown, cells displayed an increased number of cellular extensions reminiscent of cell differentiation. There was also an increase in apoptosis, associated with increased p21Cip1/WAF1 expression that was independent of p53. These results suggest that HDACs, especially HDAC2, are important enzymes involved in the early events of carcinogenesis, making them candidate markers for tumor progression and targets for cancer therapy.
 ...
PMID:Inhibition of histone deacetylase 2 increases apoptosis and p21Cip1/WAF1 expression, independent of histone deacetylase 1. 1566 16

Cervical cancer, a potentially preventable disease, remains the second most common malignancy in women worldwide. Human papillomavirus is the single most important etiological agent in cervical cancer, contributing to neoplastic progression through the action of viral oncoproteins, mainly E6 and E7, which interfere with critical cell cycle pathways, p53 and retinoblastoma. However, evidence suggests that human papillomavirus infection alone is insufficient to induce malignant changes and that other host genetic variations are important in the development of cervical cancer. This article will discuss the latest molecular profiling techniques available and review the published literature relating to their role in the diagnosis and management of cervical dysplasia and cancer. It is hoped that these techniques will allow the detection of novel biomarkers at DNA, RNA, microRNA and protein levels, which may ultimately play a role in facilitating early disease diagnosis and in predicting response to therapies, thus allowing the development of personalized treatment strategies.
 ...
PMID:Molecular profiling of cervical neoplasia. 1651 81

Senescence and apoptosis are two key mechanisms that protect against cancer development. Many cell cycle regulators, such as p14(ARF), p15(INK4b) and p16(INK4a), are important in G1 cell cycle arrest and oncogene-induced senescence. The bcl-2 protein is one of the key components that control apoptosis, while the p53 protein plays key roles in both mechanisms. The genes of these key regulator proteins are often mutated or deleted in various malignancies. It is unknown how senescence and apoptosis are regulated in one of the most common tumors of the female genital tract, cervical squamous cell carcinoma (SCC). In this study the, expression of senescence, apoptosis and proliferation markers in normal cervical epithelium, cervical intraepithelial neoplasia (CIN) and SCC are characterized via immunohistochemical staining for p14(ARF), p15(INK4b), p16(INK4a), bcl-2, p53 and Ki-67 in tissue microarray blocks containing 20 samples each of normal cervix, moderate-to-severe cervical dysplasia (CIN II-III) and invasive SCC. Samples are derived from 60 total cases of cervical biopsies and cervical conizations. Results showed that the proliferation marker, Ki-67, is markedly increased, and the senescence markers, p15(INK4b), p16(INK4a) and p14(ARF) are overexpressed in both dysplasia and carcinoma. P53 immunostain is negative in all normal cervical tissue, and positive in dysplasia and carcinoma. Although the expression of bcl-2 is increased in dysplasia, this marker is negative in approximately half of SCC cases. These results suggest that some senescence pathways are activated and are still maintained in cervical dysplasia and carcinoma. However proliferation is increased and carcinogenesis is not thwarted, leading to eventual development of cervical cancer. Other mechanisms, such as those that account for the apparent overexpression of p53 and paradoxical loss of bcl-2 expression in some SCC cases, as well as additional senescence and apoptotic pathways, may play key roles carcinogenesis of cervical SCC.
 ...
PMID:Senescence and apoptosis in carcinogenesis of cervical squamous carcinoma. 1763 54


1 2 Next >>