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 etiology of malignant melanoma has been intensely studied over the last decade. Much of the recent work focuses on oncongenes and tumour suppressor genes and the role of apoptosis in melanoma. Loss of tumour suppressor proteins such as p16 has been documented in melanoma and correlates with tumour progression. Mutations in the tumour suppressor p53 have also been documented in melanoma. The proto-oncongene Bcl-2 encodes a protein that inhibits apoptosis. Bcl-2 is found in normal melanocytes and benign nevi. However, lower levels are seen in melanoma. To investigate the relationship between melanoma and nevi, in our Basic and Clinical Science section, Dr. Radhi examines the expression of p53, p16, and Bcl in malignant melanoma arriving in benign nevi. P53 immunoreactivity was found only in the malignant component, with no expression being seen in the benign components of the lesion. This suggests that this tumour suppressor gene is involved in the pathogenesis of melanoma.
 ...
PMID:The etiology of malignant melanoma. 1057 55

The p16 gene, encodes a key checkpoint protein p16 in the cell cycle, has been reported inactivation in a wide variety of human cancers. We have previously demonstrated high frequency of p16 alterations in primary nasopharyngeal carcinoma (NPC), xenografts and cell lines. The finding implied that inactivation of the p16 gene may play an important role in the NPC development. To investigate the tumour suppressor function of p16 in NPC, we transfected p16-deficient NPC cell line, NPC/HK-1, with a wild-type p16 expression construct, and evaluated growth and tumorigenic properties of the clones stably expressing exogenous p16. Expression of the exogenous wild-type p16 significantly inhibited cell growth by more than 70% when compared to that of the parental and empty vector-transfected cells. This growth inhibition was attributable to a significant proportion of p16-expressing cells arrested at G1 phase in the cell cycle as revealed by flow cytometric analysis. By anchorage-independent colony forming assay, we found that the ability to form colonies in soft agar was highly reduced in cells expressing p16. NPC/HK1 cells expressing functional p16 also showed suppressed tumorigenicity in athymic nude mice. Taken together, our results provide strong evidence for a tumour suppressor role of p16 in NPC.
 ...
PMID:Inhibiting tumorigenic potential by restoration of p16 in nasopharyngeal carcinoma. 1058 71

Acral lentiginous melanoma is a particularly aggressive melanocytic lesion but, due to its comparative rarity, biological investigations into the behaviour of this subtype of melanoma are lacking. The activity of the recently described p16 tumour suppressor gene, thought to be the 'familial melanoma gene', was studied in 24 patients with subungual melanoma and 44 patients with plantar melanoma. Lower levels of p16 oncoprotein were demonstrated than that found in other histogenetic types of melanoma. Stratification of patients of all disease stages revealed a poorer survival in patients with low p16 expression (log rank test, chi(2)= 3.9, P = 0. 05). These data suggest that p16 inactivation may play an important role in the development and progression of acral lentiginous melanomas. However, the level of p16 expression was not prognostic since survival analysis on stratification of stage I patients according to p16 level did not reach statistical significance for both survival and disease free interval.
 ...
PMID:An analysis of p16 tumour suppressor gene expression in acral lentiginous melanoma. 1065 49

Pancreatic cancer represents the fourth leading cause of cancer death in men and the fifth in women. Prognosis remains dismal, mainly because the diagnosis is made late in the clinical course of the disease. The need to improve the diagnosis, detection, and treatment of pancreatic cancer is great. It is in this type of cancer, in which the mortality is so great and the clinical detection so difficult that the recent advances of molecular biology may have a significant impact. Genetic alterations can be detected at different levels. These alterations include oncogene mutations (most commonly, K-ras mutations, which occur in 75% to more than 95% of pancreatic cancer tissues), tumour suppressor genes alterations (mainly, p53, p16, DCC, etc.), overexpression of growth factors (such as EGF, TGF alpha, TGF beta 1-3, aFGF, bTGF, etc.) and their receptors (i.e., EGF receptor, TGF beta receptor I-III, etc.). Insights into the molecular genetics of pancreatic carcinogenesis are beginning to form a genetic model for pancreatic cancer and its precursors. These improvements in our understanding of the molecular biology of pancreatic cancer are not simply of research interest, but may have clinical implications, such as risk assessment, early diagnosis, treatment, and prognosis evaluation.
 ...
PMID:Molecular biology of pancreatic cancer; oncogenes, tumour suppressor genes, growth factors, and their receptors from a clinical perspective. 1066 Apr 90

The role of two important tumour suppressor genes, p16 and p53, was evaluated in cartilaginous tumour tissues. Genomic DNA from 22 chondrosarcomas, 5 benign chondroid tumours, 1 sample of reactive proliferative cartilage and 2 samples of normal cartilage were analysed using polymerase chain reaction, single strand conformational polymorphism, DNA sequencing and methylation-specific polymerase chain reaction. The p16 gene was found to be partly methylated in 5 high-grade chondrosarcomas and homozygously deleted in 1 chondrosarcoma. Moreover, a polymorphism was detected in 3 malignant tumours, but not in benign tumours or normal cartilage. Analysis of the p53 gene revealed an unchanged structure in all samples. These findings show a role for p16, but not p53, in chondrosarcoma.
 ...
PMID:Changes of the p16 gene but not the p53 gene in human chondrosarcoma tissues. 1070 95

The FHIT gene is located at a chromosomal site (3p14.2) which is commonly affected by translocations and deletions in human neoplasia. Although FHIT alterations at the DNA and RNA level are frequent in many types of tumours, the biological and clinical significance of these changes is not clear. In this study we aimed at correlating loss of Fhit protein expression with a large number of molecular genetic and clinical parameters in a well-characterized cohort of non-small-cell lung cancers (NSCLCs). Paraffin sections of 99 non-small-cell carcinomas were reacted with an anti-Fhit polyclonal antibody in a standard immunohistochemical reaction. Abnormal cases were characterized by complete loss of cytoplasmic Fhit staining. The Fhit staining results were then correlated with previously obtained clinical and molecular data. Fifty-two of 99 tumours lacked cytoplasmic Fhit staining, with preserved reactivity in adjacent normal cells. Lack of Fhit staining correlated with: loss of heterozygosity (LOH) at the FHIT 3p14.2 locus, but not at other loci on 3p; squamous histology; LOH at 17p13 and 5q but not with LOH at multiple other suspected tumour suppressor gene loci; and was inversely correlated with codon 12 mutations in K-ras. Fhit expression was not correlated overall with a variety of clinical parameters including survival and was not associated with abnormalities of immunohistochemical expression of p53, RB, and p16. All of these findings are consistent with loss of Fhit protein expression being as frequent an abnormality in lung cancer pathogenesis as are p53 and p16 protein abnormalities and that such loss occurs independently of the commitment to the metastatic state and of most other molecular abnormalities.
 ...
PMID:Loss of Fhit expression in non-small-cell lung cancer: correlation with molecular genetic abnormalities and clinicopathological features. 1073 5

Meningiomas are common primary brain tumours frequently presenting with deleted and/or mutated NF2 gene located on 22q.1p has been reported as the second most commonly deleted chromosomal region in these neoplasms. A new member of the INK4 family of CDK inhibitors, the p18INK4c gene, has recently been mapped to this chromosomal arm. By virtue of its structural and functional similarities with the p16 gene, p18 has been implicated as a tumour suppressor gene in a variety of cancers. In this paper 40 human meningiomas were analysed for loss of heterozygosity (LOH) at the p18 locus, mutations and inactivating methylation of the p18 gene. LOH at D1S193, D1S463 and D1S211 microsatellite marker loci mapped to 1p32 was detected in 13 of 35 (37%), four of 20 (20%), and six of 24 (25%) tumour samples, respectively. One sample presented with homozygous deletion at D1S193. Mutational analysis using single stranded conformational polymorphism (SSCP) and direct sequencing did not detect any missense mutation but revealed a novel silent mutation, G to T, at coding nucleotide 435. Analysis of HgaI, BsaHI, ScrFI and Eco0109I restriction sites of p18 exon 1 revealed absence of inactivating methylation. Immunohistochemistry with p18 monoclonal antibody detected presence of cytoplasmic p18 staining in 21 of 22 examined samples. One sample did not stain and was shown to carry homozygous deletion at D1S193. Despite the high frequency of LOH at 1p32 microsatellite markers, the lack of genetic and epigenetic aberrations in the p18 gene together with the presence of p18 protein in all but one meningioma samples argues against the role of p18 as a tumour suppressor gene important for meningioma development.
 ...
PMID:Molecular analysis of alterations of the p18INK4c gene in human meningiomas. 1073 68

An initiating role for RAS oncogene mutation in several epithelial cancers is supported by its high incidence in early-stage tumors and its ability to induce proliferation in the corresponding normal cells in vitro. Using retroviral transduction of thyroid epithelial cells as a model we ask here: (i) how mutant RAS can induce long-term proliferation in an epithelial cell in contrast to the premature senescence observed in fibroblasts; and (ii) what is the "clock" which eventually triggers spontaneous growth arrest even in epithelial clones generated by mutant RAS. The early response to RAS activation in thyroid epithelial cells showed two features not seen in fibroblasts: (i) a marked decrease in expression of the cyclin-dependent kinase inhibitor (CDKI) p27(kip1) and (ii) the absence of any induction of p21(waf1). When proliferation eventually ceased (after up to 20 population doublings) this occurred despite undiminished expression of mutant RAS and was tightly correlated with a return to the initial high level of p27(kip1) expression, together with the de novo appearance of p16(ink4a). Importantly, neither the CDKI changes nor the proliferative life span of RAS-induced epithelial clones was altered by induction of telomerase activity through forced expression of the catalytic subunit, hTERT, at levels sufficient to immortalize human fibroblasts. These data provide a basis for cell-type differences in sensitivity to RAS-induced proliferation which may explain the corresponding tumor-type specificity of RAS mutation. They also show for the first time in a primary human cell model that a telomere-independent mechanism can limit not only physiological but also oncogene-driven proliferation, pointing therefore to a tumour suppressor mechanism additional, or alternative, to the telomere clock.
 ...
PMID:Evidence for a telomere-independent "clock" limiting RAS oncogene-driven proliferation of human thyroid epithelial cells. 1089 5

Carcinogenesis is the result of a series of genetic mutations resulting in unregulated growth of a clone of cells and the development of malignant lesion that is largely monoclonal though, with the evolution of further genetic changes, there develops a degree of heterogeneity in the tumour. DNA technology, especially allelic imbalance (loss of heterozygosity) studies have identified chromosomal changes in oral carcinoma and head and neck squamous cell carcinoma (SCCHN), suggestive of the involvement of tumour suppressor genes (TSGs), particularly in chromosomes 3, 9, 11 and 17. The regions most commonly identified have included 3p, especially 3p14.2 (FHIT); 3p24, and 3p21.3, where the TSGs involved are as yet unidentified; 9p21 where p16 (INK4A/MTS-1] is the main target TSG; and 17p13 where p53 is the major target TSG. Over-expression of oncogenes, genes mainly involved in cell signalling, especially those on chromosome 11 (PRAD-1 in particular) and 17 (H-ras) and mutations in DNA repair genes, have also been implicated in the carcinogenesis of SCCHN.
 ...
PMID:Genetic aberrations in oral or head and neck squamous cell carcinoma 2: chromosomal aberrations. 1089 69

Human T-cell lymphotropic virus type-1 (HTLV-1) is aetiologically associated with adult T-cell leukaemia/lymphoma (ATL). HTLV-1 infection can also lead to various non-malignant diseases, for example, HTLV-1 associated myelopathy/tropical spastic paraparesis and HTLV-1 uveitis. HTLV-1 is endemic in southern Japan and the Caribbean. HTLV-1 infection is mainly transmitted by either breast-feeding, sexual intercourse or blood transfusions. Primary prevention of HTLV-1 in endemic areas by screening of blood and by refraining from breast-feeding have been successful. The incidence of ATL is rather low among HTLV-1 carriers (<5%). The precise mechanism of development of ATL remains unknown. It is a multiple-step process which does not require viral expression in the later stages of leukaemogenesis. Many samples have mutations of the tumour suppressor genes, p53 and/or p16(INK4A). Four subtypes of ATL have been identified, each having distinctive clinical features. Monoclonal integration of HTLV-1 proviral DNA into tumour cells is found in each of the subtypes. At present, no effective therapy for ATL exists.
 ...
PMID:Human T-lymphotropic virus type 1 infection. 1094 23


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>