Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43146 (tumour suppressor)
 5,935 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of the present study was to assess a possible role of the tumour suppressor gene p53 in neuroendocrine (Merkel cell) carcinoma of the skin with regard to tumour development and tumour progression. p53 was investigated in a series of routinely processed Merkel cell carcinomas, with application of four different p53 antibodies (CM-1, PAb1801, DO7, and PAb240) to 25 carcinomas and screening for p53 mutations of exons 4-8 by single-strand conformation polymorphism (SSCP) analysis in 9 cases. All 25 tumours in the present series showed the characteristic microscopic and immunohistochemical features of Merkel cell carcinoma of the skin. In 5 of the 25 Merkel cell carcinomas investigated 5-10% of tumour cell nuclei showed a positive p53 reaction with at least one anti-p53 antibody. A few scattered p53 positive nuclei were found in an additional 9 cases. The remaining 11 cases completely lacked p53 immunostaining. SSCP analysis of exons 4-8 revealed no significant alterations in the mobility shift of the single strand DNAs in the five cases with 5-10% p53-immunoreactive tumour nuclei or in five cases lacking p53 accumulation significant. Our results suggest that alterations of the p53 gene play only a minor part in the development or progression of Merkel cell carcinoma of the skin.
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PMID:p53 abnormalities are rare events in neuroendocrine (Merkel cell) carcinoma of the skin. An immunohistochemical and SSCP analysis. 909 81

The Japanese have a much lower incidence of nonmelanoma skin cancers (NMSCs) than Caucasians, presumably due in part to their skin type conferring relative protection from ultraviolet light radiation (UVR). To examine the contribution of environmental or endogenous mutagens other than UVR, which are expected to be relatively more important to the overall burden of NMSCs in the Japanese, we directly sequenced exons 5-8 of the p53 tumour suppressor gene in 29 Japanese patients with Bowen's disease, an in situ squamous-cell carcinoma of the skin. We found 9 mutations, including two CC:GG to TT:AA tandem transitions (presumably related to UVR), 3 transversions and 4 frameshift mutations. The mutational spectrum seen in our study contrasts with that we previously found in Bowen's disease from a Caucasian population, in keeping with a different aetiology for Bowen's disease in the respective populations. The unexpectedly high prevalence of frameshift mutations suggests that environmental mutagens other than UVR that preferentially induce deletion or insertion mutations may play an important role in the tumorigenesis of Japanese Bowen's disease, and warrants further investigation.
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PMID:p53 mutation spectrum in Japanese Bowen's disease suggests a role for mutagens other than ultraviolet light. 913 70

As dermatologists, we have all been active in educating patients about sun awareness and sun protection. This is even more important for children, as childhood exposure to ultraviolet light is a significant risk for both melanoma and nonmelanoma skin cancers. The importance of an educational approach in appropriate sun awareness in childhood is further underscored by the recent findings by Rivers et al., in the Vancouver Moles Cohort study, presented at the 1999 American Academy of Dermatology meeting. In a placebo-controlled trial, the findings of Rivers et al. clearly demonstrated that the use of sunscreens can significantly decrease the formation of nevae in children, providing further evidence to support sun awareness education initiatives. The lead article by Gooderham and Guenther in the Basic and Clinical Sciences section evaluates the effectiveness of a particular sun awareness program, and gives valuable insights into how more effective approaches may be used in the future. In addition to ultraviolet light playing a causal role in cutaneous malignancies, it is known to induce a number of other skin problems. One particularly difficult group of disorders is the photosensitive dermatoses, including solar urticaria. Bissonnette et al. describe an innovative approach to the management of refractory solar urticaria with plasma exchange. In the Grand Rounds section, Strauss et al. review the case of an acute SLE and give an insightful discussion related to bullous eruptions in acutely ill children. The mechanism of ultraviolet-light-induced carcinogenesis involves UV-induced DNA damage. Over the past decade, it has become clear that tumour suppressor genes can regulate these processes. In the Review section, Tron et al. discuss the role of the suppressor gene p53, which is mutated or lost in nonmelanoma skin cancer. P53 is crucial in protecting keratinocytes from the harmful effects of ultraviolet radiation, and in their instructive article, these authors use gene-targeted mutant mice lacking p53 to further evaluate the role in UV-induced DNA damage. With the warm weather upon us, we are spending more time in the outdoors and, as a result, are exposed to a vast number of environmental onslaughts. These include such things as Rickettsial disease, summarized in our CME section Summary Notes. Furthermore, in a comprehensive review, Dr. Sasseville examines another outdoor threat as he delineates the wide spectrum of plant contact dermatitis. This represents an important and in-depth reference on phytodermatitis. Our specialty, and indeed all of medicine, is being dramatically altered by recent advances in our understanding of disease at a molecular level. This new understanding of disease has led to the potential of modifying gene expression through the use of gene therapy. This is particularly attractive in skin disease, where gene therapy can be delivered quite readily through the skin. This advancement is insightfully discussed in the article by Somani et al., "Gene Therapy and Dermatology," which is both valuable for the cognoscenti and noncognoscenti alike, and serves as an important reference work in this area.
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PMID:Editorial 1038 44

A region from exon 4 to 8 of the tumour suppressor gene p53 was analysed in 60 feline tumours (30 fibrosarcomas, seven malignant histiocytomas, three lymphosarcomas, five basal cell tumours, five squamous cell carcinomas, two adenocarcinomas of tubular skin glands, one undifferentiated carcinoma of the skin, seven mammary carcinomas). Missense mutations were detected in two fibrosarcomas, one malignant fibrous histiocytoma, the undifferentiated carcinoma of the skin and one mammary carcinoma. One nonsense mutation was detected in one fibrosarcoma and one deletion/frameshift-mutation was observed in one squamous cell carcinoma.
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PMID:Presence of p53 mutations in feline neoplasms. 1068 60

Although much less prevalent than its nonmelanoma skin cancer counterparts, cutaneous malignant melanoma (CMM) is the most lethal human skin cancer. Epidemiological and biological studies have established a strong link between lifetime exposure to ultraviolet (UV) light, particularly sunburn in childhood, and the development of melanoma. However, the specific molecular targets of this environmental carcinogen are not known. Data obtained from genetic and molecular studies over the last few years have identified the INK4a/ARF locus as the "gatekeeper" melanoma suppressor, encoding two tumour suppressor proteins in human, p16 $^{\text{INK4a}}$ and p $14^{\text{ARF}}$ . Recent developments in molecular biotechnology and research using laboratory animals have made a significant gene breakthrough identifying the components of the p16 $^{\text{INK4a}}$ /Rb pathway as the principal and rate-limiting targets of UV radiation actions in melanoma formation. This review summarizes the current knowledge of the molecular mechanisms involved in melanoma development and its relationship to sunlight UV radiation.
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PMID:Towards a Better Understanding of the Molecular Mechanisms Involved in Sunlight-Induced Melanoma. 1568 39