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

Small DNA tumour viruses, such as simian virus 40 (SV40), papilloma viruses and adenoviruses, encode proteins that form complexes with and inactivate the p53 and retinoblastoma (RB) proteins. This convergent evolution reflects the common need of these viruses to inactivate these two important regulators of cell cycle progression and cell survival. Polyomavirus, a close relative of SV40, is different. Its large T protein complexes only with RB, not with p53. We have examined whether this is compensated by the frequent appearance of p53 mutations in polyomavirus-induced tumours. We tested the p53 status of 15 polyomavirus-induced sarcomas. Two sarcomas were p53-negative while six carried mutant p53. Another six sarcomas expressed low levels of wild-type p53. One tumour expressed high levels of wild-type p53 protein as shown by DNA sequencing and immunofluorescence staining. MDM2 amplification was not detected in any of the tumours, but Northern blotting showed that MDM2 was overexpressed in at least two tumours that expressed wild-type p53 and in one tumour that expressed both wild-type and mutant p53. Treatment with the DNA-damaging agent mitomycin C caused p53 protein accumulation followed by induction of MDM2 and WAF1/p21 mRNA in four of the tumours expressing wild-type p53, indicating that p53-mediated transcriptional activation was unaltered in these tumours. However, p53-mediated transactivation of WAF1/p21 was impaired in the wild-type p53-expressing tumours that expressed elevated levels of MDM2. These results demonstrate that p53 mutation and inactivation are frequently but not invariably involved in polyomavirus-induced tumorigenesis.
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PMID:Role of p53 mutation in polyomavirus-induced tumorigenesis. 912 63

Loss of heterozygosity and microsatellite instability have been often reported in breast cancer and seldom in proliferative breast disease (PBD). DNA samples from microdissected PBD lesions, including papillomas (25 lesions), from 8 women were analyzed by polymerase chain reaction for loss of heterozygosity and microsatellite instability at 10 loci including INT-2 oncogene locus, D17S796 (the p53 gene region), and D17S579 (in the region of the BRCA-1 gene). In a patient, five loci with microsatellite instability and two loci with loss of heterozygosity were identified in one papilloma with florid hyperplasia and atypia, and 10 other PBD lesions were negative for genetic alteration (GA) and atypia. Three loci with microsatellite instability were identified in another PBD lesion without atypia, whereas another lesion from this second patient had minimal atypia without GAs. These two patients have been well for more than 20 years. No other patient, including a woman developing cancer, had GAs. We detected GAs in PBD (25% of women, 8% of lesions). Incomplete correlation between GAs and anatomic atypia was suggested. It seems evident that several GAs in PBD lesions may not indicate clinically meaningful premalignancy for remaining breast.
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PMID:Loss of heterozygosity and microsatellite instability in breast hyperplasia. No obligate correlation of these genetic alterations with subsequent malignancy. 917 86

P53 is overexpressed in more than 50% of all human cancers. A previous study suggested that p53 was also overexpressed in oral papillomas. This study was carried out to investigate whether p53 expression was correlated with expression of the cellular proliferation marker Ki-67 and the epithelial differentiation marker cytokeratin-4 (CK4) in oral papillomas. Formalin-fixed paraffin-embedded sections of 30 oral papilloma specimens and 30 unmatched normal oral mucosal specimens were processed for immunohistochemistry, using an avidin-biotin-peroxidase procedure and monoclonal antibodies. A semiquantification analysis on p53 and Ki-67 labeling indices was performed. Twenty-eight of 30 (93%) papilloma specimens were positive for p53. The percentage of p53-positive cells in the basal layer was 60.4 +/- 14.8 (mean +/- SD, n = 28), and that of Ki-67-positive cells was 26.7 +/- 14.4. There was no correlation between expression of p53 and that of Ki-67. Expression of CK4 was inversely correlated with the expression of Ki-67 but not correlated with the expression of p53.
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PMID:Expression of p53, Ki-67 and cytokeratin-4 (CK4) in oral papillomas. 917 72

The incidence of point mutations of H-, K- and N-ras and p53 oncogenes in male BALB/c mouse stomach tumors induced with N-methyl-N-nitrosourea (MNU) was examined by direct sequencing and PCR single-strand conformation polymorphism (PCR-SSCP). A mutation of GGT to AGT at K-ras codon 12 was found by SSCP in one adenocarcinoma from a total of 19 specimens including 5 adenocarcinomas, 9 adenomatous hyperplastic regions, 1 squamous cell carcinoma and 4 normal-like stomach regions from 4 mice. No mutations were detected by direct sequencing of H-, K- and N-ras oncogenes at exons 1 (codons 12 and 13) and 2 (codon 61) in a total of 26 specimens comprising 10 adenocarcinomas, 10 adenomatous hyperplastic regions, 2 squamous cell carcinomas and 4 normal-like stomach regions from 6 mice. No mutations were detected by direct sequencing of p53 oncogene at exons 5, 6, 7 and 8 in a total of 30 specimens including 13 adenocarcinomas, 8 adenomatous hyperplastic regions, 2 squamous cell carcinomas, 1 papilloma and 6 normal-like stomach regions from 7 mice. These results suggest that ras and p53 oncogenes do not play a role in mouse stomach carcinogenesis induced by MNU.
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PMID:Rare occurrence of ras and p53 gene mutations in mouse stomach tumors induced by N-methyl-N-nitrosourea. 919 27

In carcinomas of the uterine cervix of which p53 is frequently inactivated by papilloma viruses, gene transfer of p21, effector of p53, is an alternative tool to suppress cell growth. We introduced the p21 gene into HeLa cells. The transfectant with p21 showed a significant growth retardation by blockage of G1 to S transfer of the cell cycle. This cell line showed significantly reduced anchorage-independent growth as well as attenuated telomerase activity. These data suggest that gene transfer of p21 is an effective tool to lead carcinoma cells with inactivated p53 into less malignant phenotype.
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PMID:Introduction of p21(Waf1/Cip1) gene into a carcinoma cell line of the uterine cervix with inactivated p53. 921 68

Chemical influences, mainly heavy tobacco smoking, chewing snuff, excessive alcohol consumption, and some occupational hazards, are known to be important etiologic factors in laryngeal carcinogenesis. The synergistic or cooperative interaction of human papilloma virus (HPV) infection with these chemical factors are serious considerations in the development of laryngeal carcinoma. With the development during the last decade of Southern blot hybridization and polymerase chain reaction (PCR), extensive and comprehensive studies have been conducted to determine the presence and biological (etiologic) significance of HPV. Developed cancer, as well as juvenile and adult multiple and single papilloma of the larynx, have been the subject of clinical and molecular-pathological investigation. Our previous study showed that cancer may develop on the basis of leukoplakia and adult-onset papilloma. Extensive kilocytes, an indication of HPV infection, can be seen by histological examination in papillomas and carcinoma. Literary data suggest that in laryngeal squamous cell carcinoma, including varicoses carcinoma, HPV 16, HPV 18, and HPV 33 DNA have been detected. Both in juvenile and adult-onset respiratory papillomatosis, patients could have either HPV type 6 or 11 DNA sequences. Molecular biological and PCR studies indicate that HPV may play an etiologic role in the development of human malignancies of the upper aerodigestive tract and uterine (cervical) origin. However, evidence that unequivocally links HPV infection with laryngeal squamous cell carcinoma is still lacking. In laryngeal cancer, p53 abnormalities are related to smoking-induced mutagenesis rather than HPV. Studies have postulated an interaction between HPV infection and chemical carcinogens and have concluded that HPV possibly are co-adjuvants during the multistage process of neoplastic transformation.
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PMID:Some etio-pathogenetic factors in laryngeal carcinogenesis. 921 6

Human papillomavirus (HPV) types 6 and 11 have been associated with benign laryngeal papilloma, while HPV-16 is occasionally associated with laryngeal carcinoma. In this study, a case of laryngeal squamous papillomas with severe dysplasia was evaluated for the presence of HPV infection. The biopsy specimens were taken from a 58-year-old female patient at two different time points 3 months apart. Architecturally, the tumor showed papillary configuration reminiscent of squamous papilloma. Cytologically, the lesion showed morphologic features characteristic of severe squamous epithelial dysplasia. HPV infection was determined by DNA in situ hybridization using type-specific HPV-DNA probes. HPV-11 probes demonstrated homogeneous nuclear staining, suggesting productive viral replication. In contrast, HPV-16 probe produced a speckled pattern, suggesting HPV-16 DNA integration. Normal laryngeal epithelium did not yield specific hybridization. The presence of HPV-11 and HPV-16 was confirmed by PCR using HPV type-specific primers. Immunocytochemical staining was performed to detect Ki-67, a proliferation marker, and p53. Ki-67 expression was demonstrated throughout the whole thickness of epithelium. Staining for p53 was negative. This study suggests that multiple HPV infections can occur in the same lesion and that HPV-16 infection and its DNA integration may contribute to the occurrence of severe dysplasia in the lesion described.
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PMID:Coinfection of HPV-11 and HPV-16 in a case of laryngeal squamous papillomas with severe dysplasia. 921 36

We report a case of inverted papilloma in the urinary bladder with special reference to its malignant potential. A 77-year-old male patient complaining of microhaematuria was subjected to cystoscopic examination, which showed a non-papillary pedunculated tumour at the postero-lateral wall, and was treated with transurethral resection. The histological findings of the specimen were compatible with inverted papilloma of the urinary bladder, except for the presence of low grade dysplastic changes in the tumour nuclei. We revealed the malignant potential of this tumour, analyzing and evaluating nuclear DNA content, proliferating cell nuclear antigen (PCNA) as well as p53 expression.
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PMID:Inverted papilloma of the urinary bladder: a case evaluated for malignant potential. 924 45

Human papilloma virus 16 (HPV 16) is associated with cervical cancer and is therefore considered a major health risk for women. Immortalization of keratinocytes induced by HPV infection is largely due to the binding of p53 and Rb by the the viral oncoproteins E6 and E7, respectively, and is driven to a large extent by a transforming growth factor alpha/amphiregulin epidermal growth factor receptor autocrine loop. In this study, we show that the growth of HPV 16-immortalized human keratinocytes can be blocked by a selective epidermal growth factor receptor kinase inhibitor, AG 1478, and by AG 555, a blocker of cyclin-dependent kinase 2 (Cdk2) activation. AG 1478 induces a massive increase in the Cdk2 protein inhibitors p27 and p21, whereas AG 555 appears to have a different mechanism of action, inhibiting the activation of Cdk2. Growth arrest induced by AG 1478 and AG 555 is accompanied by up to 20% of cells undergoing apoptosis. Following AG 1478 treatment but not AG 555 treatment, up to 50% of cells undergo terminal keratinocyte differentiation as determined by filaggrin expression and by the decline in the expression of cytokeratin 14. The growth-arresting properties of AG 1478 and AG 555 identifies them as possible lead antipapilloma agents.
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PMID:Inhibitors of epidermal growth factor receptor kinase and of cyclin-dependent kinase 2 activation induce growth arrest, differentiation, and apoptosis of human papilloma virus 16-immortalized human keratinocytes. 928 82

p53 gene mutation is documented in head and neck cancer. No reports exist relating this mutation to normal mucosa or benign and malignant lesions of the nasal cavity. We investigate p53 overexpression using immunohistochemical techniques improved by an antigen retrieval method. p53 protein was analyzed in the following cases: normal, benign [papilloma and inverted papilloma (IP)] and malignant [squamous-cell carcinoma (SCC) arising in IP, SCC alone, adenocarcinoma and small-cell carcinoma]. Both the intensity and rate of positive p53 immunostaining were evaluated using a quantitative Auto-CAD program. Overexpression of p53 protein was not identified in normal mucosa, benign or premalignant lesions; however, approximately 60% is correlated to nasal cancer. p53 overexpression correlates with heavy smoking. Both the IP and SCC portions of SCC synchronous with IP showed similar p53 immunoreactivity. SCC arising in IP shows a lower p53 immunoreactivity than SCC alone. Thus, smoking along with a p53 mutation may be a mutagenic agent in nasal cancers. Alteration of the p53 protein may play an important role in the early stages of the malignant transformation of IP. A low p53 immunoreactivity indicates the presence of wild-type p53 protein. This may show a better response to radiation therapy yielding a better prognosis for SCC arising in IP compared to SCC alone. However, further clinical trials are required to investigate this possibly worthwhile prognostic marker.
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PMID:Assessment of p53 protein expression in normal mucosa and benign and malignant lesions of the nasal cavity. 949 92


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