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).
Br J Dermatol 1992 Dec
PMID:Mutant p53 oncogene expression in keratoacanthoma and squamous cell carcinoma. 833 63

In the present study, we investigated the expression of the tumour suppressor protein p53 in 113 primary and 43 metastatic malignant melanomas by immunohistochemistry, and correlated the findings with clinicopathological parameters such as histological melanoma subtype, thickness of primary melanomas (Breslow thickness) and patient outcome. In primary melanomas, the polyclonal anti-p53 antibody CM-1 detected immunoreactivity in 70% of the lesions, predominantly in the cytoplasm. Signals were observed in this cellular compartment in 57% of the melanomas, whereas in 32% nuclear p53 over-expression was detected. Immunohistochemistry, using the monoclonal antibody DO-1, revealed lower staining frequencies. However, both antibodies showed congruent results in approximately 80% of the cases. Overall, immunoreactivity was observed in 73% of superficial spreading melanomas, but only in 52% of lentigo maligna melanomas. This difference (P < 0.001) was mainly due to a lower frequency of cytoplasmic immunoreactivity (P < 0.002). There was no difference with respect to cytoplasmic and nuclear immunoreactivity between thin (< 1 mm thickness) and thicker primary melanomas. Staining frequencies detected in metastatic lesions seemed to be lower than in primary tumours. In 103 primary melanomas, follow-up data for at least 5 years were available. In 71% (54 of 76) of the primary melanomas which did not recur, and in 78% (21 of 27) of tumours with subsequent metastases, p53 over-expression was detected by CM-1. However, this difference was not statistically significant. The results of the present study indicate that immunoreactivity to anti-p53 antibodies is a common observation in malignant melanomas, with staining signals predominantly found in the cytoplasm of cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Br J Dermatol 1995 Jul
PMID:Expression of p53 protein in malignant melanoma: clinicopathological and prognostic implications. 766 36

The p53 protein is the product of a tumour suppressor gene, which is implicated in many human malignancies. p53 expression was investigated by immunohistochemistry in a series of viral warts (n = 12) from five patients with epidermodysplasia verruciformis (EV), using a monoclonal anti-p53 antibody (DO7). p53 expression was also investigated in a series of common warts (n = 8), flat warts (n = 8), and penile bowenoid papulosis (n = 6) from non-EV patients. Immunostaining was positive in 11 of 12 (92%) EV warts, whereas p53 reactivity was negative in most cases of warts from non-EV patients. Exons 5-8 of the p53 gene were screened by the polymerase chain reaction-single strand conformation polymorphism technique in four EV warts, which were strongly stained for p53, and p53 mutations were not detected. These results suggest an association between p53 accumulation (probably of wild type) and EV warts.
Br J Dermatol 1995 Apr
PMID:p53 protein expression in viral warts from patients with epidermodysplasia verruciformis. 874 64

It is currently widely accepted that the tumour suppressor gene p53 is critically involved in the proliferation and differentiation of tumour cells including melanoma cells. In the present study, we examined 60 cases of primary melanoma to compare the expression of p53 protein with conventional prognostic markers for melanoma such as clinical and histological parameters. No correlation was found between the p53 protein and clinical factors except for the presence of a metastatic node and development to clinical stage II. However, the expression of p53 protein was significantly associated with tumour thickness over 1.5 mm, levels IV and V of invasion, the presence of ulceration, and high mitotic rate for 5-year survival rate. Although many questions still remain to be answered, our results and those of others for various other malignant tumours, implicate p53 in malignant transformation of pigment cells. Indeed, it could be a new marker for an unfavourable prognosis of malignant melanoma, even though the gene mutation in this highly lethal tumour has yet to be established.
Arch Dermatol Res 1995
PMID:Expression of the p53 protein in malignant melanomas as a prognostic indicator. 776 85

Lysyl oxidase (EC 1.4.3.13), a copper-dependent enzyme which catalyses the formation of aldehyde cross-links, and acts primarily on collagen and elastin, is known to be increased during wound healing and in fibrotic disorders including liver cirrhosis and atherosclerosis, and to be decreased in some hereditary connective tissue diseases and in malignant cell lines. A recent study showed that lysyl oxidase might possess tumour suppressor activity as an antioncogene for ras. Little is known about the localization of this enzyme in human skin. In this study, we determined immunohistochemically the localization of lysyl oxidase in normal skin of young and elderly subjects obtained from sun-exposed and unexposed regions of the body. All skin samples tested had similar distributions of lysyl oxidase. The enzyme was present both extracellularly and intracellularly. Extracellularly, a few granular aggregates of immunoreactants were observed along collagen and elastic fibres. These granules were more common in the adventitial portion of the dermis than in the reticular portion. Of all sun-exposed and unexposed regions studied, the skin of the face displayed the greatest amount of extracellular immunoreactants. Immunopositive granules were observed intracellularly in fibroblasts, vascular endothelial cells, sweat glands, sebaceous glands, arrector pili muscles and some keratinocytes. These findings provide evidence that, as suggested in recent reports, lysyl oxidase may have a variety of intracellular functions.
Br J Dermatol 1994 Sep
PMID:Immunohistochemical localization of lysyl oxidase in normal human skin. 791 5

This article reviews the contribution of modern investigative techniques to the diagnosis of cutaneous lymphoproliferative diseases. Special attention is given to the significance of immunoglobulin and T-cell receptor rearrangements; as detected by Southern blotting and/or the polymerase chain reaction. Additional topics discussed include immunohistochemistry, cytogenetics, onco- and tumour suppressor genes and in-situ hybridization. It is recommended that the results of these techniques are interpreted in the form of a multifaceted diagnostic profile.
Semin Dermatol 1994 Sep
PMID:Review of investigative diagnostic techniques for cutaneous lymphoma. 798 84

Expression of the tumour suppressor protein, p53, was determined in 77 cutaneous melanocytic lesions, and in five lymph node metastases from malignant melanoma, in an immunohistochemical study employing CM-1, an antiserum raised against recombinant human p53 protein. Because wild-type p53 protein is rapidly degraded in normal cells, p53 immunoreactivity suggests the presence of an abnormally stable p53 protein. This may occur through either post-translational mechanisms or gene mutation. A highly significant correlation was found between p53 immunoreactivity and malignancy in melanocytic lesions (P < 0.0001). Overall, p53 immunoreactivity was observed in 63% of tumour specimens examined, but not in benign melanocytic naevi, although occasional foci of weak nuclear p53 immunoreactivity were observed in a minority of dysplastic naevi and a solitary Spitz naevus. A significant correlation was also found between strong p53 immunoreactivity and malignant melanomas associated with a poor prognosis (P = 0.008). These data suggest an important role for p53 tumour suppressor protein in the biology of human cutaneous malignant melanoma.
Br J Dermatol 1993 Jun
PMID:p53 immunoreactivity in human malignant melanoma and dysplastic naevi. 833 44

p16INK4 gene, which encodes a specific inhibitor of cyclin-dependent kinase 4 (CDK4), has been recently reported as an important tumour suppressor gene. It is mapped to chromosome 9p21, which is frequently deleted or mutated in many tumour cell lines including malignant melanoma. Since the CDK4/cyclin D complex propels a cell to go through the G1 check point of the cell cycle, a critical phase of cell division, alteration of the p16INK4 gene could lead a cell to uncontrolled proliferation and malignant transformation. To clarify any role for p16INK4 and CDK4 proteins in the development of human malignant melanoma, we have examined, immunohistochemically, the expression of these two proteins in melanocytic neoplasms including 19 primary lesions of non-familial melanoma. Intense nuclear and/or cytoplasmic expression of the CDK4 protein was observed in 11 of 19 cases (58%) of melanoma. In contrast, virtually no nuclear or cytoplasmic staining for CDK4 protein was detected in 28 benign melanocytic naevi, including six Spitz naevi. Expression of p16INK4 protein was observed in three of 19 melanomas (16%) and in 17 of 28 benign naevi (61%). Inverse expression of CDK4 and p16INK4, at individual cell level, was detected in one case of melanoma. The present study suggests that CDK4 overexpression is characteristic for malignant melanoma, and probably reflects its autonomous accelerated cell proliferation. The expression rate of p16INK4 protein in malignant melanoma was lower than that in benign naevi, although the significance of p16INK4 deletion in melanoma development has not been definitely confirmed.
Br J Dermatol 1996 Feb
PMID:Immunohistochemical detection of CDK4 and p16INK4 proteins in cutaneous malignant melanoma. 874 40

Two cases of Werner's syndrome are reported. Fibroblasts derived from both patients revealed reduced population doubling numbers. Chromosomal analyses for fibroblasts from both patients and lymphocytes from one patient revealed that chromosomal aberrations occur frequently and randomly. Although some of the chromosomal aberrations involved sites where tumour suppressor genes have been mapped, neither of our patients demonstrated malignancy. Chromosomal aberration at one critical site may not be sufficient to induce cancer or additional factors may be necessary.
Br J Dermatol 1997 Apr
PMID:Werner's syndrome--chromosome analyses of cultured fibroblasts and mitogen-stimulated lymphocytes. 915 73

There is increasing concern about the adverse health effects associated with the use of sunbeds, particularly with respect to skin photocarcinogenesis. The induction of mutagenic DNA damage is a prerequisite for the development of skin tumours, and it is well established that direct types of damage such as cyclobutane pyrimidine dimers (CPDs) give rise to mutations in tumour suppressor genes and oncogenes. In addition, ultraviolet radiation may induce indirect types of DNA damage, including oxidative products, which are also potentially mutagenic. By using specific DNA repair enzymes (T4 endonuclease V and endonuclease III) and the comet assay we have been able to detect the induction of CPDs, oxidized or hydrated pyrimidine bases and single-strand breaks in cultured human fibroblasts (MRC-5) after exposure for between 15 s and 20 min on two different commercial sunbeds containing Philips 'Performance' 100W-R or Philips TL80W/10R lamps. The ratio of endonuclease III to T4 endonuclease V sensitive sites varied substantially between the two lamps and was 3.3% and 18%, respectively. The sunbed containing the 'Performance' 100W-R lamps was as potent at inducing CPDs as was natural sunlight in fine weather. These results establish that commercial tanning lamps produce the types of DNA damage associated with photocarcinogenesis in human cells, and complement epidemiological evidence indicating the potential risk of using sunbeds.
Br J Dermatol 1997 Nov
PMID:Induction of mutagenic DNA damage in human fibroblasts after exposure to artificial tanning lamps. 941 25


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