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)

Even though the "low-risk" human papillomavirus (HPV) diseases, such as condyloma acuminatum, rarely progress to malignancy, their high incidence evidences the need for a better understanding of molecular interactions between these viruses and the epithelium. Our study examined the contribution of altered expression of certain cytokines and antioncogenes to the hyperproliferative properties of HPV-related skin lesions. The "low-risk" human papillomavirus types (HPV 6 or 11) were determined by in situ hybridization and PCR amplification followed by direct sequencing using consensus primers from the highly conserved L1 region in six different condylomas. mRNA levels of certain cytokines (e.g., TGF-beta 1, IFN-beta), tumor suppressor genes (RB, p53), c-myc, epidermal growth factor receptor, and cdc2 kinase were measured by RT/PCR. A characteristic change in mRNA levels of those genes was found in condylomas compared to that of the expression levels of uninfected skin. Western blot experiments demonstrated a higher proportion of the hyperphosphorylated form of RB protein and a higher level of cdc2 kinase and c-myc, but low p53 and TGF-beta 1 levels in condylomas. These data reflect a higher proliferative state of those condylomas compared to the normal skin, suggesting a direct or indirect involvement of "low-risk" HPVs in interaction with the cellular cytokine/antioncogene system providing growth advantage to those infected cells.
 ...
PMID:Alterations in cytokine/antioncogene expression in skin lesions caused by "low-risk" types of human papillomaviruses. 816 33

The importance of epidermal growth factor receptor (EGF-R) as an immunohistochemical factor of prognosis has been investigated in 820 cases of breast carcinoma irrespective of subtyping. An immunohistochemical membrane positivity for EGF-R (Ab1, clone 455 and Ab2, clone 528, Oncogene Science Manhasset NY, USA, ABC-peroxidase method) has been observed in neoplastic cells of 131/820 breast carcinomas (15.9%); the percentage is lower than those of the majority of reported series, but the total number of cases is higher. A significant inverse relationship between EGF-R and estrogen/progesterone receptors has been found (ER-ICA, PgR-ICA, Abbott, PAP-method). Highly proliferating Ki67 positive (> = 20% stained nuclei-Dakopatts Denmark) and oncoprotein p53 (Pab 1801 clone, Oncogene Science) positive carcinomas are more frequently EGF-R positive (p < 0.001). No relationship exists between EGF-R expression, c-erbB-2 (3B5 clone, Oncogene Science) expression, tumor size and lymph node status. The detection of EGF-R may be a useful addition to other immunohistochemical prognosticators, but it must be related with clinical outcome in further studies.
 ...
PMID:Relationships between epidermal growth factor receptor (EGF-R) and other predictors of prognosis in breast carcinomas. An immunohistochemical study. 817 Jul 12

Ionizing radiation (XRT) is often used to treat squamous cell carcinoma of the tongue (SCCT) but little is known of its genetic effects on surviving cancer cells. The effect of XRT on p53, epidermal growth factor receptor (EGFR), and transforming growth factor alpha (TGF alpha) tumor marker expression was evaluated using immunohistochemical analysis in 79 patients with SCCT. Sixty-six patients received no radiation, while 13 received XRT before surgery. Radiation did not influence EGFR or p53 expression. TGF alpha expression, however, was significantly decreased in radiated tumors (15% versus 43%, P = 0.04). These data suggest that XRT either decreases the expression of TGF alpha in SCCT (suggesting a genetic alteration in surviving cancer cells), or does not kill cancer cells with decreased TGF alpha expression. In the latter case, diminished TGF alpha expression may serve as a marker of radioresistance.
 ...
PMID:Radiation treatment decreases transforming growth factor alpha expression in squamous carcinoma of the tongue. 818 Sep 57

Abnormalities of the p53 gene and protein were examined in 81 primary breast carcinoma samples. Using a polymerase chain reaction-single-strand conformational polymorphism (PCR-SSCP) analysis, mutations in p53 exons 5-8 were identified in 13 of 81 tumours (16 per cent) and confirmed by DNA sequencing. Positive staining for p53 protein was detected in ten of 77 (13 per cent) of these tumours using polyclonal CM1 antibody on formalin-fixed tissue. Mutations detected by PCR-SSCP analysis were more common in grade III tumours (P = 0.015), but no correlation was found with tumour size, node status or level of epidermal growth factor receptor expression. A p53 mutation was associated with positive antibody staining in only two patients. Positive immunohistochemical staining using a p53 antibody may detect p53 protein expression, but this may not correlate directly with an underlying mutation in the hot spot region examined.
 ...
PMID:Correlation between p53 mutations and antibody staining in breast carcinoma. 792 74

Esophageal carcinomas from 24 patients, most of whom were smokers and consumed alcoholic beverages daily, were analyzed for mutations in exons 5-8 of the p53 tumor suppressor gene. Mutations were identified by polymerase chain reaction amplification and direct sequencing in 12 of 24 (50%) of the samples; almost half of the mutations were at A:T base pairs. Nuclear accumulation of p53 protein, determined by immunohistochemistry with the CM-1 polyclonal antibody, was observed in all cases in which a missense mutation in the p53 gene was detected. None of the 24 carcinomas had amplification of the mdm2 gene, an alternate pathway to p53 loss of function. Alterations involving three other cancer-related genes associated with human esophageal carcinogenesis, c-erbB-1/epidermal growth factor receptor (EGFR), c-myc, and retinoblastoma (Rb), were examined by Southern blot or immunohistochemical analysis in the same sample set to explore the possibility of a link between oncogene activation and loss of tumor suppressor function. While no associations were observed between amplification of the c-myc or EGFR genes and p53 abnormalities, a significant correlation (P < 0.01) was seen between the presence of p53 mutation and EGFR overexpression. Absence of Rb protein, measured immunohistochemically, was observed in four tumors, none of which had aberrations of the p53 gene.
 ...
PMID:Correlation of p53 mutations with epidermal growth factor receptor overexpression and absence of mdm2 amplification in human esophageal carcinomas. 828 Mar 79

The role of bcl-2 expression in solid tumours is as yet undefined. It was, therefore, the purpose of this study to investigate expression of bcl-2 protein in 111 human breast carcinomas using immunohistochemistry and the monoclonal antibody bcl-2 124. Expression was then compared with the established indicators of prognosis and biological behaviour in malignant breast disease. No relationship could be observed between bcl-2 and node status, tumour size, differentiation, type or age at excision. However, a strong positive relationship was seen between bcl-2 and oestrogen receptor (ER), with 70 of 88 (80%) bcl-2-positive tumours being ER positive also, compared with seven of 23 (30%) bcl-2-negative tumours being ER positive (P < 0.0001). The converse was found when bcl-2 was compared with epidermal growth factor receptor (EGFR). A strong negative relationship was observed, with 26 of 88 (30%) bcl-2-positive tumours being EGFR positive, compared with 16 of 23 (70%) bcl-2-negative tumours being EGFR positive (P = 0.001), raising the possibility that bcl-2 is an ER-regulated gene. An inverse relationship was also found between bcl-2 and the oncogenes c-erbB-2 and p53. Thus, loss of bcl-2 expression in breast cancer is associated with a range of molecular markers of poor prognosis and may define part of an ER-negative, EGFR-positive phenotype.
 ...
PMID:bcl-2 in normal human breast and carcinoma, association with oestrogen receptor-positive, epidermal growth factor receptor-negative tumours and in situ cancer. 828 95

The development of a malignant tumor generally entails a series of events that damage the genome of a somatic cell and result in the malignant phenotype. These events chronicle the malignant progression of a tumor; a dynamic process in which more aggressive and growth-deregulated cell populations are constantly evolving. Gliomas, the most common primary tumors of brain, are known to become increasingly malignant with time. Within recent years, several details of the molecular genetic events associated in their progression have been determined. The earliest events of glioma progression include loss of genetic information from the long arms of chromosomes 13 or 22, or the short arm of chromosome 17 for which targeting of the TP53 (p53) gene has been indicated. Loss of a single complement of type I interferon (IFN) genes from 9p and loss of genetic information from 19q are seen in the tumors of intermediate malignancy grade. Events associated with the most malignant of glial tumors include loss of the second, type I IFN gene complement, loss of genetic information from chromosome 10, and gene amplification (most commonly the epidermal growth factor receptor, in 40% of cases). These findings have helped elucidate the events associated with glial tumorigenesis, and through the identification of specific genes, have provided a starting point for investigating the molecular biology of central nervous system neoplasia.
 ...
PMID:Gene and chromosomal alterations associated with the development of human gliomas. 834 89

In an attempt to define the type and temporal sequences of somatic genetic changes that precede the onset of invasive lung cancer, and to search for biological markers useful in screening multiple primary tumors of the upper aerodigestive tract, we have performed a cytogenetic and genetic study using normal bronchial epithelium and primary tumor specimens of 68 patients undergoing pulmonary resection for early stage lung cancer, and normal bronchial epithelium of 5 controls with metastatic sarcomas. Of the 68 lung cancer cases, 31 had a single tumor and 37 displayed multiple synchronous or metachronous tumors. Cytogenetic alterations were observed in 59% (23/39) of the evaluable tumor specimens with complex rearranged karyotypes, particularly involving chromosomes 3 (70%), 17 (39%), 11 (26%), 8, 9, 12 (22%), and 7 (17%). Gene alterations were also detected including overexpression of epidermal growth factor receptor (EGFR) in 63% (36/57), HER2/NEU in 21% (12/56), and p53 mutations in 50% (12/24). The overall frequency of genetic changes (any type) in the tumors was 76% (52/68). In the normal bronchial mucosa, we identified a rearranged karyotype in 20% of the evaluable cases (13/63); particularly simple rearrangements involving chromosomes 3p (6 cases), 7 (6 cases), 17 (3 cases), 9, 11 (2 cases), 8 (1 case); as well as overexpression of EGFR in 39% (20/51) and of HER2/NEU in 14% (7/51). The overall frequency of genetic changes (any type) in the normal epithelium was 46% (30/65). The presence of a rearranged karyotype in the bronchial mucosa was associated with a rearranged karyotype in the tumor sample. Other statistically significant correlations were found between histopathologic and clinical features and the occurrence of the different cytogenetic and genetic changes both in tumors and in the normal bronchial mucosa. No genetic abnormalities were found in the bronchial epithelium of the 5 controls.
 ...
PMID:Genetic changes in lung cancer. 841

The discovery of peptide growth factors and cancer-causing genes (oncogenes and tumor-suppressor genes) has provided us with the exciting opportunity to begin to understand the molecular pathology of human ovarian cancer. Activation of several genes, including HER-2/neu, myc, ras, and p53 have been described in some ovarian cancers. In addition, some protooncogenes such as the epidermal growth factor receptor (erbB) and the M-CSF receptor (fms) are expressed along with the respective ligands (peptide growth factors) in some ovarian cancers. Although the studies reviewed in this paper represent a promising beginning, we remain far from a comprehensive understanding of growth regulation and transformation of human ovarian epithelium.
 ...
PMID:Growth regulation and transformation of ovarian epithelium. 842 Jun 75

The incidence of primary brain tumors has increased dramatically among elderly North Americans during the past two decades. Numerous chromosomal abnormalities have been associated with these tumors; various subsets of these abnormalities are specific to certain types of brain tumors. Astrocytic gliomas may exhibit losses of genetic information from chromosomes 9p, 10q, 11p, 13q, 17p, or 22. Mutations of the p53 gene are found mostly in the malignant astrocytic forms and have been linked to malignant tumor transformation and progression. Functional and structural abnormalities of the neurofibromatosis 1 (NF1) gene and overexpression of the epidermal growth factor receptor have been associated with expression of the malignant glioma phenotype. Other less clearly defined abnormalities in astrocytomas include mutations of the retinoblastoma (RB) gene and overexpression of platelet-derived growth factor; transforming growth factor-alpha and -beta; the c-erb B-1, c-myc, ras, c-fos, and ros oncogenes; and insulin-like growth factor I and II. In other glioma tumors, p53 mutations are either infrequent, as in oligodendrogliomas, or absent, as in ependymomas. Occasionally, medulloblastomas exhibit p53 mutations and loss of genetic information from chromosomes 6q and 16q or expression of the c-erb B-2 oncogene. Loss of heterozygosity in chromosome 22 is the most frequent event in meningiomas, suggesting the presence of a tumor-suppressor gene in this chromosome.
 ...
PMID:Epidemiology, cytogenetics, and molecular biology of brain tumors. 849 8


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>