UNIPROT:P43146 - FACTA Search

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Query: UNIPROT:P43146 (tumour suppressor)
5,935 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The degree of DNA-instability as revealed by the immunohistochemical staining with anti-single-stranded DNA antibody after acid hydrolysis (DNA-instability test) was used as a marker of malignancy. This was applied to mild dysplasia (42 cases), moderate dysplasia (43 cases), severe dysplasia (27 cases), squamous cell carcinoma in situ (CIS) (21 cases), invasive squamous cell carcinoma (SCC) (31 cases) and normal (7 cases) human uterine cervix. The expression of tumour suppressor gene p53 and oncogene bcl-2 was detected immunohistochemically. Proliferative activity was evaluated by PCNA immumohistochemistry and the quantitative analysis of the number, mean area, the largest area and maximum shape irregularities of AgNOR in a nucleus were performed for all these cases. The distribution of numeric chromosomal aberrations of chromosome 17 was also investigated in some of these cases. The results showed that 31 SCC (100%), 21 CIS (100%), 21 severe dysplasia (77.77%), 28 moderate dysplasia (65.11%), and 14 mild dysplasia (33.33%) were positively stained by the DNA-instability test diffusely or sporadically, indicating their malignancy. Reflecting the malignant character, these cases showed a remarkable increase in the PCNA-index with the loss of polarity of PCNA positive cell distribution and also an increase in number, mean and largest sizes and maximum shape irregularity of AgNOR dots. The mean chromosome index for chromosome 17, p53 and bcl-2 immunostaining positivity were also found to be significantly increased in moderate and severe dysplasia and in cancerous cases in comparison to normal and mild dysplasia cases. Moreover, the DNA-instability-test positive dysplasia cases showed statistically significant increased values of PCNA-index, AgNOR parameters, mean chromosome index, p53 and bcl-2 expression in comparison to those of DNA-instability-test negative dysplasia cases. In conclusion, some mild dysplasia (33.33%) and most of the moderate (65.11%) and severe dysplasia (77.77%) were regarded as malignant in nature, existing at an early stage of progression of malignancy.
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PMID:Early progression stage of malignancy of uterine cervical dysplasia as revealed by immunohistochemical demonstration of increased DNA-instability. 1096 62

Bcl-2 family member proteins are differentially expressed in skin and in non-melanoma skin cancer (NMSC). To elucidate the contribution of bcl-2 and bax proteins to epidermal differentiation and skin carcinogenesis, we investigated keratinocyte proliferation, differentiation and tumourigenesis in bcl-2(-/-) and bax(-/-) mice. The rate and pattern of proliferation and spontaneous cell death in the bcl-2(-/-) and bax(-/-) mice were not different from control mice. The epidermis of bcl-2(-/-) and bax(-/-) expressed sightly higher levels of cytokeratin 1 and loricrin compared to control littermates. The apoptotic response to ultraviolet-induced genotoxic stress was assessed by quantitating TUNEL positive cells. Bax(-/-) keratinocytes showed a significant resistance to UV-induced cell death compared to control mice. The life-span of bcl-2(-/-) mice precluded an assessment of bcl-2 gene disruption on in vivo tumourigenesis. A significant increase in tumour incidence was observed in bax(-/-) mice compared to control mice in two-step chemical carcinogenesis studies. These findings suggest that bcl-2 and bax gene products may be important determinants of normal keratinocyte differentiation and response to genotoxic stress in vivo, and indicate that bax may provide a tumour suppressor effect during skin carcinogenesis.
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PMID:Bax gene disruption alters the epidermal response to ultraviolet irradiation and in vivo induced skin carcinogenesis. 1117

beta-Catenin has an essential role in intercellular adhesion and signal transduction. beta-catenin functions as a transcriptional activator downstream in the Wnt signalling pathway. Cytoplasmic stabilisation of beta-catenin, mainly due to inactivating mutations of the adenomatous polyposis coli (APC) tumour suppressor gene or activating mutations in exon 3 of the beta-catenin gene, can activate this important pathway in the development of several carcinomas. To determine whether this pathway for malignant transformation is important in oesophageal cancer, we analysed 39 primary oesophageal squamous cell carcinomas (OSCC). Immunohistochemical expression of beta-catenin was studied in formalin-fixed, paraffin-embedded tissue samples. Results were correlated with clinicopathological parameters and immunohistochemical expression of the proteins p53, E-cadherin, bcl-2 and Ki-67. All examined OSCC had beta-catenin expression localised in the cellular membrane, frequently with a heterogeneous pattern. Seven (18%) cases also showed immunoexpression in the cytoplasm and nuclei of the tumour cells. These seven tumours were localised in the upper (three) or in the middle third (four) of the oesophagus. Only one patient had p53 expression and all had bcl-2 expression. The consensus sequence for glycogen synthase kinase (GSK) 3beta phosphorylation in exon 3 of the beta-catenin gene was studied using polymerase chain reaction and direct sequencing in the seven cases with nuclear beta-catenin expression. No genetic alteration was found. These results suggest that beta-catenin expression may characterise a subset of OSCC.
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PMID:beta-catenin expression pattern in primary oesophageal squamous cell carcinoma. Relationship with clinicopathologic features and clinical outcome. 1119 70

Several genetic alterations have been implicated in the development of malignant melanoma, but the expression of oncogenes, tumour suppressor, mismatch repair and apoptosis-related genes and their interactions in melanoma have not been completely clarified. We simultaneously examined the expression of p73, c-erbB-2, ras, p53, Mdm2, p27, DCC, hMLH-1, hMSH-2, bcl-2, Bax and NF-kappaB, by immunocytochemistry, in both primary and metastatic melanoma cell lines derived from melanoma patients. p73 was expressed in 7/8 cell lines, but stronger expressed in the metastatic cells than in the primary melanoma cells. c-erbB-2 was detected in all 8 cell lines and ras in 2/5 metastases. p53 was found in all the cell lines and Mdm2 in 1/8 of the cell lines. In the same patient, the intensity of p27 expression was decreased from the primary to the metastatic tumours. bcl-2 was expressed in all the cell lines. Bax was absent in 5/8 cell lines. In the same patient, Bax was weakly expressed in the primary tumour but lacking in the metastases. The data demonstrate that overexpression of p73, c-erbB-2, p53 and bcl-2, and loss of Mdm2 and Bax may interact and play important roles in the development and aggressiveness of human melanoma.
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PMID:Expression of oncogenes, tumour suppressor, mismatch repair and apoptosis-related genes in primary and metastatic melanoma cells. 1171 83

The loss of tumour suppressor genes (TSGs) is a key event in many human cancers, including gastric carcinoma. Many TSG candidates have been studied, but their roles in gastric carcinogenesis remain unclear. To clarify the clinical significance of TSG expression in gastric carcinoma, the expression of various TSG candidates (p53, E-cadherin, FHIT, smad4, rb, VHL, PTEN, MGMT, p16, and KAI1), as well as other proteins (bcl-2, MUC1, MUC2, MUC5AC, MUC6, CEA, CD44, beta-catenin, C-erbB2, and cyclin B2), was evaluated immunohistochemically in 329 consecutive gastric carcinomas using the tissue array method. The overexpression of p53 and MUC1 (p < 0.01) and the loss of expression of smad4 (p = 0.04), FHIT (p = 0.03), MGMT (p = 0.01), E-cadherin, KAI1, and PTEN (p < 0.01) were found to be significantly associated with poor gastric carcinoma prognosis. Seven out of eight survival-associated proteins were found to be protein products of TSGs. The gastric carcinomas were divided into five groups according to the grade of alteration in TSG expression. No TSG expression loss was found in 32 cases (TSG1). One TSG loss was found in 47 cases (TSG2), two in 67 cases (TSG3), three or four in 64 cases (TSG4), and five, six, or seven in 38 cases (TSG5). The grade of TSG expression was confirmed to be significantly associated with WHO classification (p = 0.04), pTNM stage, lymphatic invasion, and patient survival (p < 0.01 for the latter three). By multivariate analysis, the grade of TSG expression was found to be significantly and independently associated with patient survival (p < 0.01). In conclusion, the findings of this study suggest that the cumulative loss of TSG expression in gastric carcinoma is important in determining patient survival.
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PMID:Tumour suppressor gene expression correlates with gastric cancer prognosis. 1269 39

Tumour growth and its progression to a metastatic phenotype involves a serious of genetic events with abnormal activation of oncogenes or inactivation of tumour suppressor genes and others genes connected with proliferation, apoptosis and neovascularisation. The aims of the study were to determine the possible prognostic value of angiogenesis, proliferation index Ki67, p53 and bcl-2 proteins expression in patients with laryngeal cancer. The group of 151 patients with laryngeal cancer, surgically treated with minimum 5 years observation, was multi-variously analysed. Paraffin--embedded tissue sections from each case were stained with a monoclonal antibody raised against FVIII antigen, p53 and bcl-2 proteins and Ki67 proliferation antigen using a peroxidase labelled streptavidin--biotin kit in standard immunohistochemistry techniques. In univariate analysis: staging IV, tumour size T4, nodal metastasis N2 and N3, local and nodal recurrences, high expression of Ki67 and P53, high (over median) IA measured as number of microvessels with FVIII expression were significantly associated with shortened overall survival. Disease-free survival was related to: proliferation index Ki67, expression of P53 protein and angiogenesis measured as microvessels density with expression of FVIII antigen. In multivariate analysis the most important death risk factors for overall survival were: tumour size, nodal metastasis, local and nodal recurrences, P53 protein expression and IA measured as number of microvessels with FVIII expression. In multivariate analysis of disease-free survival only P53 protein expression, proliferative index Ki67 and expression of FVIII had independent prognostic value. Intensity of angiogenesis, proliferation index of Ki67 antigen and expression of P53 protein were independent predictors of patients with laryngeal cancer outcome. In contrary Bcl2 protein seems to be useless in these patients.
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PMID:[Survival of patients with laryngeal cancer and some prognostic factors]. 1452 74

Endometrial adenocarcinoma is the most common malignant neoplasm of the female genital tract and, despite its relative frequency, the molecular events that contribute to the development and progression of the lesion remain poorly understood. The normal human endometrium is characterized by hormone-dependent variations during the menstrual cycle. This tightly controlled system is disturbed in endometrial hyperplasia and carcinomas and a series of changes initiate and promote progression towards the malignant phenotype. These changes can be subdivided into discrete steps, involving activation of oncogenes, inactivation of tumour suppressor genes, deregulation of cell cycle regulators or other proteins involved in tumour invasion and progression. Immunohistochemical expression of different biomarkers such as hormone receptor status (ER, PR), proliferation associated indices (PCNA, MIB1), oncogene (c-erbB-2), tumour suppressor gene products (pRb, p53 protein), cell cycle related proteins (cyclin D1, cyclin E, p21/WAF1), anti-apoptotic protein (bcl-2), adhesion molecule (CD44s), proteolytic enzyme (cathepsin D), heat shock protein (hsp27) and metallothionein (MT) has shown the contribution of these molecules to endometrial carcinogenesis in a hormone-dependent or independent manner as an early or late event. In addition, these biomarkers seem to be correlated with tumour differentiation or myometrial invasion, and therefore could be considered as indicators of the biological behaviour of endometrial carcinoma. Furthermore, the interrelationships of these molecular markers show that these genetic dysregulations could be implicated in the control of cell proliferation and differentiation, and thereby in the multistep process of endometrial carcinogenesis.
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PMID:Immunohistochemical tumour markers in endometrial carcinoma. 1612 80

Microcystins (MCs) are hepatotoxic cyclic heptapeptides produced by freshwater cyanobacteria. They are inhibitors of serine/threonine protein phosphatases 1A and 2A and are involved in liver tumour promotion. Several recent studies indicated that MCs are genotoxic and may also act as tumour initiators. Based on our previous results showing that microcystin-LR (MCLR) induces DNA damage in HepG2 cells, we have now explored the effect of MCLR on the expression of selected genes known to be involved in the cell response to DNA damage and apoptosis. The HepG2 cells were exposed to non-cytotoxic concentrations (0.01, 0.1 and 1 microg/ml) of MCLR for various periods of time (2-16 h) and the mRNA expression was determined with the quantitative real-time polymerase chain reaction (QRT-PCR). We found a significantly elevated expression of tumour suppressor gene p53 and its downstream-regulated genes involved in DNA repair and cell cycle regulation (p21, gadd 45a, mdm2), as well as increased expression of the pro-apoptotic gene bax, but no alterations of the anti-apoptotic bcl-2. Up-regulation of the expression of mdm2, p21 and gadd45a provides strong support for our previous suggestion that MCLR is a genotoxic carcinogen. The increased ratio of expression of bax to that of bcl-2 induced by MCLR suggests that apoptosis in HepG2 cells proceeds via the mitochondrial pathway.
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PMID:Patterns of microcystin-LR induced alteration of the expression of genes involved in response to DNA damage and apoptosis. 1819 Nov 68

A total of 20 pancreatic biopsy samples taken from Fibrocalculous Pancreatopathy previously known as Fibro Calculus Pancreatic Diabetes (FCPD) patients, a variant of Malnutrition Related Diabetes Mellitus (MRDM) or under 30 young diabetes attending hepatobiliary, surgical and out patient department of Bangladesh Diabetes, Endocrine and Metabolic (BIRDEM) hospital were processed for light microscopic examination. Four samples were subjected to Immunohistochemistry (IHC) staining using antibodies to T cell marker (CD3), B cell marker (CD20), anti apoptotic markers (bcl-2) and tumour suppressor gene marker p53. Light microscopic findings and IHC indicate an immune mediated injury of pancreatic tissue and increased evidence of apoptosis which possibly results in the development of diabetes in these patients.
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PMID:Histopathological changes of pancreas in patients with fibrocalculous pancreatopathy. 1862 56

Prostatic apoptosis response-4 (Par-4) was first identified in prostatic cancer cells that were induced to undergo apoptosis. Recently, Par-4 has been suggested to be a tumour suppressor gene that plays a role in the development of endometrial carcinomas (ECs), but the exact mechanism remains to be clarified. Here we examined gene activation signalling cascades and influence on cell kinetics during endometrial tumourigenesis. In normal endometrium, constitutively high levels of Par-4 expression were observed in epithelial cells through the menstrual cycle, in contrast to the transient up-regulation in stromal components in the menstrual stage, correlated positively with the phospho-p65 (pp65) status and apoptosis. In contrast, most ECs exhibited significant down-regulation as compared to normal endometrium, with positive links only to pp65 expression. In EC cell lines, transfection of the NF-kappaB subunit p65 led to transactivation of Par-4 through specific binding to its promoter region, in contrast to the suppression by active Akt, suggesting that the balance between the two signals may be important to determine Par-4 expression levels. In addition, transient overexpression of Par-4 resulted in the induction of not only apoptosis but also senescence, through changes in the expression of bcl-2 and p21$;{{\rm WAF1}}$, respectively. Together, these findings suggest that a signalling cascade involving sequential activation of NF-kappaB/p65 and Par-4 may participate in relatively early events of endometrial tumourigenesis, leading to modulation of cell kinetics including apoptosis and cell cycle progression.
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PMID:Transcriptional regulation of pro-apoptotic Par-4 by NF-kappaB/p65 and its function in controlling cell kinetics during early events in endometrial tumourigenesis. 2018 24

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