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 tumour suppressor gene p53, located on the short arm of chromosome 17, encodes for a nuclear protein which regulates cell proliferation by inhibiting cells entering S-phase. p53 mutations are alleged to be the commonest genetic abnormality in human cancer. We studied mutant p53 oncoprotein expression, using PAb1801 monoclonal antibody immunohistochemistry, in 25 'ideal' keratoacanthomas and 26 well-, 19 moderately and 18 poorly differentiated squamous cell carcinomas of the skin. While there was a highly significant trend in the proportion of p53 oncoprotein-positive lesions from keratoacanthomas to poorly differentiated squamous cell carcinomas (chi 2 = 17.13, df = 1, exact P = 0.00003), p53 expression was inadequate for distinguishing keratoacanthoma from well-differentiated squamous cell carcinoma (chi 2 = 2.55, df = 1, exact P = 0.18; corresponding to a sensitivity of 0.84 and a specificity of only 0.36).
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PMID:Mutant p53 oncogene expression in keratoacanthoma and squamous cell carcinoma. 833 63

An inverse correlation has been demonstrated between nm23 gene expression and metastasis. The gene is located on chromosome 17q (q1.1-q2.1), a region distinct from tumour suppressor gene p53. We have previously reported expression of mutant products of p53 gene to be significantly associated with worsening degrees of differentiation in squamous cell carcinoma. nm23 gene product, which shows complete identity to human erythrocyte nucleoside diphosphate kinase, was used to raise an affinity-purified polyclonal antibody Ab-11 which is applicable to formalin-fixed and paraffin-embedded tissues. Keratoacanthomas and squamous cell carcinomas of the epidermis form a fascinating human tumour model in which to test the hypothesis that the nm23 gene confers 'anti-metastatic' properties, since the former never metastasise while the latter have this potential. Two observers rated immunohistochemistry for the nm23 gene product as the proportion of tumour positive from grades 1-4 (corresponding to 25, 50, 75 and 100% of tumour cells stained). Nineteen typical keratoacanthomas, 20 well, 21 moderately and 8 poorly differentiated epidermal squamous cell carcinomas were studied. The Jonckheere-Terpstra test statistic of association between staining grade and lesion type was 762.5, p = 0.189 (2 tails), p = 0.0945 (1 tail). There was no statistically significant trend in tumour staining from keratoacanthoma through decreasing grades of differentiation of squamous cell carcinoma. nm23 product expression does not appear to correlate with differentiation, itself an indicator of metastatic potential, in this system of human squamous cell neoplasms.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:'Anti-metastatic' nm23 gene product expression in keratoacanthoma and squamous cell carcinoma. 835 13

Non-melanoma skin cancer (NMSC) is by far the most frequently diagnosed cancer in Australia, and exposure to ultraviolet (UV) radiation is the primary cause. Both UVB and UVA radiation have been shown to cause DNA damage and immunosuppression, the important forms of biological damage that lead to NMSC. The DNA of keratinocytes absorbs UV radiation and produces photolesions such as cyclobutane pyrimidine dimers (CPDs). UV absorption by other chromophores results in the production of reactive oxygen species which cause oxidative damage to DNA such as 8-oxo-7,8-dihydroguanine (8oxoG). These photolesions can then, if not correctly repaired, lead to signature mutations. Reactive oxygen species also cause receptor activation and damage lipids and proteins. UV also deprives cells of adenosine triphosphate, and causes inflammation and cell cycle dysregulation. UV radiation has been shown to exert potent immunosuppressive effects on the skin through a number of molecular and cellular mechanisms. Many tumour suppressor genes and oncogenes have been studied and implicated in photocarcinogenesis, particularly p53, PTCH1, BRM and RAS. Clinical observations, histological analysis, as well as molecular and cytogenetic studies have shown actinic keratoses (AKs) and Bowen's disease (BD) to be precursors of squamous cell carcinomas (SCCs). Keratoacanthomas (KAs), a type of SCC, and AKs have frequently been observed to regress. Sun protective measures and sunscreens can reduce the incidence of NMSCs, although their effectiveness is limited by non-compliance. A large number of chemopreventive agents have been investigated, but to date none has been found to be clinically useful except within selected high risk groups. Therefore, further research is urgently required to find an ideal chemopreventive agent that is effective, safe, accessible and convenient.
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PMID:Non-melanoma skin cancer: carcinogenesis and chemoprevention. 2347 34