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)

We studied p53 over-expression in a series of 42 primary penile carcinomas (seven verrucous carcinomas, 14 well-differentiated, 15 moderately-differentiated and six poorly-differentiated squamous cell carcinomas) from Chinese patients using the p53 protein specific mouse monoclonal antibody DO-7 on paraffin sections. p53 protein was detected in 40% (17 cases) of the tumours. The p53 staining was not observed in the penile warts (n = 6) and verrucous carcinomas (n = 7). Positive p53 staining was identified only in the less differentiated tumour cells in the periphery of the tumour cell nests in all the cases. The non-invasive dysplastic epithelium next to the tumours could also be positive for p53 protein (three out of 10 cases in which the dysplastic epithelium adjacent to the tumour was adequately sampled). Furthermore, 100% of the human papillomavirus (HPV)-positive cases showed positive p53 staining. It is concluded that p53 over-expression is present in penile squamous cell carcinomas and adjacent non-invasive tumour cells. An inverse correlation between HPV and p53 gene mutation is not observed in penile cancers.
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PMID:Expression of p53 and its relationship with human papillomavirus in penile carcinomas. 863 6

The E6 oncoprotein of human papillomavirus (HPV) is known to inactivate the control function on cell cycle exerted by p53 tumor suppressor protein in vitro by binding to p53 and thus facilitating the degradation of p53. We have applied a simultaneous in situ demonstration method for detecting p53 protein and HPV-DNA on formalin-fixed tissue sections, and investigated the in vivo interrelationship of p53 protein and HPV-DNA. Immunohistochemical staining for p53 protein with polyclonal and monoclonal antibodies, recognizing both wild-type (wt) and mutated p53 protein, was performed first and in situ DNA hybridization (ISH) for HPV types 6/11 or 16/18 with digoxigenin-labelled probes thereafter. 47% (25/53) of 48 histologically confirmed primary or recurrent condylomata acuminata (CA), 2 Bowenoid papulosis (BP) and 3 common wart (CW) biopsies, positive for HPV 6/11 or HPV 16/18 DNA, showed keratinocytes immunopositive for p53 protein. Of these, 11 lesions with abundant numbers of p53-positive cells were further analyzed with the double method. Signals for abnormal p53 protein and HPV-DNA were detected in separate cell nuclei in all biopsies and, additionally, in the same cell nuclei in 3 biopsies (1 BP, 1 CA, 1 CW). Usually the p53 positivity localized more basally in the epidermis than HPV-DNA, although p53- and HPV-positive keratinocytes were always located closely. The findings were similar for HPV-types 6/11 and 16/18. Our finding of both p53 and HPV-6/11 signals in the same cell nuclei may indicate complexing of p53 and low-risk HPV's without degradation of p53. Our results show abnormal p53 expression in HPV-infected skin lesions, and suggest that p53 protein is susceptible to aberrations even in the cells in the vicinity of productive HPV infection. However, it is not yet fully understood how HPV interferes with p53 protein in these cells.
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PMID:Simultaneously detected aberrant p53 tumor suppressor protein and HPV-DNA localize mostly in separate keratinocytes in anogenital and common warts. 873 14

p53 immunoreactivity was examined in 132 cutaneous non-melanoma tumours from renal transplant recipients and in 114 histologically matched specimens from immunocompetent individuals. Skin lesions examined included 52 viral warts, 50 dysplastic keratoses, 51 intraepidermal carcinomas (IEC), 50 invasive squamous cell carcinomas (SCC) and 43 basal cell carcinomas (BCC). Overall, 51% (51/101) pre-malignant skin lesions and 45% (42/93) non-melanoma skin cancers (NMSC) showed p53 immunoreactivity, with extensive (> 50% cells positive) p53 staining in 27% (27/101) of pre-malignant and 20% (19/93) of malignant lesions. 17% (9/52) viral warts showed p53 immunoreactivity, but this was limited to focal or basal p53 staining. p53 immunoreactivity in all tumours was less in transplant than in non-transplant patients and this reached statistical significance for SCCs (p = 0.03).
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PMID:p53 immunoreactivity in non-melanoma skin cancer from immunosuppressed and immunocompetent individuals: a comparative study of 246 tumours. 879 57

The papillomavirus family represents a remarkably heterogeneous group of viruses. At present, 77 distinct genotypes have been identified in humans and partial sequences have been obtained from more than 30 putative novel genotypes. Geographic differences in base composition of individual genotypes are generally small and suggest a low mutation rate and thus an ancient origin of today's prototypes. The relatively small size of the genome permitted an analysis of individual gene functions and of interactions of viral proteins with host cell components. Proliferating cells contain the viral genome in a latent form, large scale viral DNA replication, as well as translation and functional activity of late viral proteins, and viral particle assembly are restricted to differentiating layers of skin and mucosa. In humans papillomavirus infections cause a variety of benign proliferations: warts, epithelial cysts, intraepithelial neoplasias, anogenital, oro-laryngeal and -pharyngeal papillomas, keratoacanthomas and other types of hyperkeratoses. Their involvement in the etiology of some major human cancers is of particular interest: specific types (HPV 16, 18 and several others) have been identified as causative agents of at least 90% of cancers of the cervix and are also linked to more than 50% of other anogenital cancers. These HPV types are considered as 'high risk' infections. Their E6/E7 oncoproteins stimulate cell proliferation by activating cyclins E and A, and interfere with the functions of the cellular proteins RB and p53. The latter interaction appears to be responsible for their mutagenic and aneuploidizing activity as an underlying principle for the progression of these HPV-containing lesions and the role of high risk HPV types as solitary carcinogens. In non-transformed human keratinocytes transcription and function of viral oncoproteins is controlled by intercellular and intracellular signalling cascades, their interruption emerges as a precondition for immortalization and malignant growth. Recently, novel and known HPV types have also been identified in a high percentage of non-melanoma skin cancers (basal and squamous cell carcinomas). Similar to observations in patients with a rare hereditary condition, epidermodysplasia verruciformis, characterized by an extensive verrucosis and development of skin cancer, basal and squamous cell carcinomas develop preferentially in light-exposed sites. This could suggest an interaction between a physical carcinogen (UV-part of the sunlight) and a 'low risk' (non-mutagenic) papillomavirus infection. Reports on the presence of HPV infections in cancers of the oral cavity, the larynx, and the esophagus further emphasize the importance of this virus group as proven and suspected human carcinogens.
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PMID:Papillomavirus infections--a major cause of human cancers. 887 33

Renal allograft recipients (RARs) have a well-documented increased incidence of viral warts and cutaneous neoplasia, particularly those with long graft life and high sun exposure. A clinicopathological survey of 69 RARs in south-east Scotland, with follow-up periods of up to 28 years after transplantation, revealed marked variation in patient susceptibility to cutaneous malignancy with concomitant variation in HPV prevalence. Skin cancers were found in 34 patients. Eight patients showed high susceptibility [defined as more than four intraepidermal carcinomas (IECs) or invasive squamous cell carcinomas (SCCs)] 42 had intermediate susceptibility (1-3 IECs or SCCs, or >3 keratoses) and 18 had low susceptibility (< or = 3 keratoses and no cancers). SCCs, IECs and keratoses from the high-susceptibility group were found to have greater prevalences of human papillomavirus (HPV) DNA (56%, 45% and 50% respectively), than SCCs (0%) and IECs (33%) from intermediate-susceptibility RARs and keratoses (36%) from the combined intermediate- and low-susceptibility groups and compared with a group of immunocompetent controls (27%, 20% and 15% respectively). No differences in p53 protein accumulation, determined immunohistochemically, were observed in tumours from the three groups. Categorization of RARs by susceptibility to cutaneous malignancy provides clinically useful information, as significantly more high-susceptibility patients (38%) developed aggressive, potentially lethal anogenital or cutaneous squamous cell cancers than did patients in the intermediate group (5%, P=0.005) or the low-susceptibility group (0%).
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PMID:Renal allograft recipients with high susceptibility to cutaneous malignancy have an increased prevalence of human papillomavirus DNA in skin tumours and a greater risk of anogenital malignancy. 904 31

Human papillomaviruses (HPVs), a large family of small DNA tumour viruses, are unequivocally linked to the induction of benign warts and anogenital cancer. Mechanisms utilized by HPV oncoproteins identify p53 and pRB as important cellular controls. New techniques reveal that novel members of the HPV family may contribute to non-melanoma skin cancer development.
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PMID:Role of human papillomaviruses in warts and cancer. 979 62

The vast majority of the human experience with viral infections is associated with acute symptoms, such as malaise, fever, chills, rhinitis and diarrhea. With this acute or lytic phase, the immune system mounts a response and eliminates the viral agent while acquiring antibodies to that specific viral subtype. With latent or chronic infections, the viral agent becomes incorporated into the human genome. Viral agents capable of integration into the host's genetic material are particularly dangerous and may commandeer the host's ability to regulate normal cell growth and proliferation. The oncogenic viruses may immortalize the host cell, and facilitate malignant transformation. Cell growth and proliferation may be enhanced by viral interference with tumor suppressor gene function (p53 and pRb). Viruses may act as vectors for mutated proto-oncogenes (oncogenes). Overexpression of these oncogenes in viral-infected cells interferes with normal cell function and allows unregulated cell growth and proliferation, which may lead to malignant transformation and tumour formation. Development of oral neoplasms, both benign and malignant, has been linked to several viruses. Epstein-Barr virus is associated with oral hairy leukoplakia, lymphoproliferative disease, lymphoepithelial carcinoma, B-cell lymphomas, and nasopharyngeal carcinoma. Human herpesvirus-8 has been implicated in all forms of Kaposi's sarcoma, primary effusion lymphomas, multiple myeloma, angioimmunoblastic lymphadenopathy, and Castleman's disease. Human herpesvirus-6 has been detected in lymphoproliferative disease, lymphomas, Hodgkin's disease, and oral squamous cell carcinoma. The role of human papillomavirus in benign (squamous papilloma, focal epithelial hyperplasia, condyloma acuminatum, verruca vulgaris), premalignant (oral epithelial dysplasia), and malignant (squamous cell carcinoma) neoplasms within the oral cavity is well recognized. Herpes simplex virus may participate as a cofactor in oral squamous cell carcinoma development by enhancing activation, amplification, and overexpression of pre-existing oncogenes within neoplastic tissues. Because of the integral role of viruses in malignant transformation of host cells, innovative antiviral therapy may prevent tumour development, involute neoplastic proliferations, or arrest malignant progression.
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PMID:Molecular piracy: the viral link to carcinogenesis. 993 Mar 54

A series of 120 biopsies from benign (verruca vulgaris and keratoacanthoma), premalignant (actinic keratosis and extragenital Bowen's disease) and malignant (squamous cell carcinoma) skin lesions were studied immunohistochemically for the expression of cell-cycle proteins p53, p21 (WAF-1), PCNA and Ki-67. The presence of human papillomavirus (HPV) DNA in these samples had been analysed previously using in situ hybridization (ISH) and PCR. Moderate to intense expression of both PCNA and Ki-67 was present in most of the lesions studied. PCNA staining was extensive in the epidermis underneath the layers where abundant HPV DNA staining was shown in HPV DNA-positive verrucas. In keratoacanthomas, p21 and PCNA expression remained low, despite intense p53 expression. In actinic keratosis, only half of the specimens showed overexpression of p53 associated with moderate or intense expression of PCNA. In extragenital Bowen's lesions, all these cell-cycle markers were overexpressed, but in squamous cell carcinomas, they were heterogeneously expressed and showed no correlation with tumour differentiation. Our results suggest a mechanism by which HPV can reactivate the host genes (leading to cell proliferation) to support its own DNA replication. Also p21 might start keratinocyte differentiation in areas where HPV DNA replication starts. Cell proliferation remained active in actinic keratosis and Bowen's lesions, emphasizing the precancer character of these lesions in contrast with the benign nature of keratoacanthoma and verruca vulgaris.
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PMID:Expression of cell-cycle proteins p53, p21 (WAF-1), PCNA and Ki-67 in benign, premalignant and malignant skin lesions with implicated HPV involvement. 1042 81

Human papillomaviruses (HPV) are increasingly recognised as important human carcinogens. The best established association with human malignancy is that of high-risk mucosal HPV types and anogenital cancer. HPV-induced transformation of anogenital epithelia has been the subject of intense research which has identified the cellular tumour suppressor gene products, p53 and pRB, as important targets for the viral oncoproteins E6 and E7 respectively. Certain HPV types are also strongly associated with the development of non-melanoma skin cancer in the inherited disorder epidermodysplasia verruciformis (EV). However, in contrast with anogenital malignancy the oncogenic mechanisms of EV-HPV types remain uncertain, and there appears to be a crucial additional requirement for ultraviolet radiation. Cutaneous HPV types in the general population are predominantly associated with benign viral warts, but a role in non-melanoma skin cancer has recently been postulated. Polymerase chain reaction based HPV detection techniques have shown a high prevalence of HPV DNA, particularly in skin cancers from immunosuppressed patients and to a lesser extent in malignancies from otherwise immunocompetent individuals. No particular HPV type has yet emerged as predominant, and the role of HPV in cutaneous malignancy is unclear at present. It remains to be established whether HPV plays an active or purely a passenger role in the evolution of non-melanoma skin cancer.
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PMID:Human papillomavirus and the development of non-melanoma skin cancer. 1047 13

An aetiological role has been proposed for human papillomavirus (HPV) in skin carcinogenesis within the immunosuppressed patient population. To examine this possibility, we have focused on an HPV type that, to date, has been identified only in the cutaneous lesions of renal transplant recipients despite a high degree of sequence homology with other HPVs commonly found in warts in the general population. We report that the non-coding region of this virus, HPV type 77, contains a consensus binding site for the tumour suppressor protein p53, and we show by gel-retardation analysis that this sequence does indeed bind p53. Furthermore, using reporter gene assays, we demonstrate that HPV77 promoter activity is stimulated by UV radiation and that this response is mediated through the p53 binding site. This is the first report of a p53-dependent positive response element within a viral genome. Our results suggest a possible novel mechanism by which specific types of HPV might act as cofactors with UV radiation in cutaneous transformation.
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PMID:The promoter of a novel human papillomavirus (HPV77) associated with skin cancer displays UV responsiveness, which is mediated through a consensus p53 binding sequence. 1050 68


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