Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is scant information on the cell proliferation, apoptosis, oncogenes, and tumor suppressor genes status in adenosis. Forty-eight foci of adenosis were studied with immunohistochemistry for MIB-1; c-erbB-2, c-erbB-3, bcl-2 oncogenes; and p53. To evaluate apoptosis, the TdT dUTP nick end labeling (TUNEL) method was applied. Results were compared with the same studies on benign prostatic hyperplasia (BPH) (n = 20), low-grade prostatic intraepithelial neoplasia (PIN) (n = 10); high-grade PIN (n = 20), Gleason sum 2 to 6 cancer (n = 16); and Gleason sum 7 to 10 cancer (n = 22). MIB-1 proliferation index was lowest in BPH, followed by adenosis, low-grade prostatic intraepithelial neoplasia (PIN), low-grade cancer, high-grade PIN, and high-grade cancer. The apoptotic rate was generally low in all groups, although it was higher in PIN and cancer. In BPH and adenosis, bcl-2 was absent in luminal cells. In low- and high-grade PIN, both basal and luminal cells expressed bcl-2, whereas in cancer, expression was found in only 1 case (3%). C-erbB-2 showed absent or low values for cancer and adenosis, whereas it was commonly expressed in BPH and low- and high-grade PIN. Low expression in adenosis was also found with c-erbB-3 (6%) compared with all other groups. Expression of p53 was confined to cancer. Despite a significantly higher proliferation index rate compared with BPH, adenosis showed a markedly lower proliferating index when compared with low-grade PIN, high-grade PIN, and cancer. Expression of the oncogenes c-erbB-2 and cerbB-3 was very low in adenosis, and the staining pattern for bcl-2 was similar to that of BPH. These results provide additional evidence to that of prior studies that adenosis is a histological small acinar proliferation more akin to BPH than high-grade PIN or adenocarcinoma.
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PMID:Cell proliferation, apoptosis, oncogene, and tumor suppressor gene status in adenosis with comparison to benign prostatic hyperplasia, prostatic intraepithelial neoplasia, and cancer. 1049 43

In vitro experiments suggest that angiotensin II (Ang II) may cause growth via angiotensin type 1 (AT(1)) receptors and apoptosis via angiotensin type 2 (AT(2)) receptors. To answer the question of whether AT(1) or AT(2) receptor activation could induce apoptosis in the vasculature in vivo, Wistar rats were infused for 7 days with Ang II (120 ng. kg(-1). min(-1) subcutaneously) and treated with the AT(2) receptor antagonist PD 123319 (30 mg. kg(-1). d(-1) subcutaneously) or the AT(1) receptor antagonist losartan (10 mg. kg(-1). d(-1) orally). Apoptosis in thoracic aorta was quantified by radiolabeled DNA laddering and by terminal deoxynucleotide transferase-mediated dUTP nick end-labeling. The expression of p53, bax, bcl-2, and caspase-3, which play critical roles in apoptotic signaling, was examined by Western blot analysis. The mRNA expression of AT(1) and AT(2) receptors was determined by reverse transcription-polymerase chain reaction. The increase in systolic blood pressure and aortic growth induced by Ang II infusion was completely prevented by losartan alone or losartan given with PD 123319, whereas PD 123319 resulted in a greater increase in systolic blood pressure and aortic growth than Ang II alone. Radiolabeled DNA laddering showed that Ang II infusion+/-losartan or PD 123319 significantly increased apoptosis (147+/-8%, 178+/-20%, and 238+/-41%, respectively, P<0.05 compared with control). Expression of bax and active forms of caspase-3 was increased in the Ang II+PD 123319 group, whereas the expression of p53 and bcl-2 was not significantly different in all groups. The expression of AT(1) and AT(2) receptor mRNA was downregulated by losartan and PD 123319, respectively. Thus, when AT(1) or AT(2) receptors are stimulated in vivo, apoptosis is enhanced in the media of blood vessels. In the case of AT(1) receptor stimulation, this may occur secondary to vascular growth and modulate the latter. Both bax and caspase-3 participate in the pathways of apoptosis triggered by in vivo AT(1) receptor stimulation.
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PMID:In vivo study of AT(1) and AT(2) angiotensin receptors in apoptosis in rat blood vessels. 1052 36

The relationship between malignant potential and apoptosis in astrocytic tumors has not been clearly defined, and further classification of astrocytic tumors is necessary. To elucidate the relationship between the histopathological grade of astrocytic tumors and apoptosis, we studied 25 cases of astrocytic tumors, comprising 10 cases of glioblastoma (GB), 7 cases of anaplastic astrocytoma (AA), and 8 cases of astrocytoma (AC). We detected apoptosis using the TdT-mediated dUTP-biotin nick-end labeling (TUNEL) method. We studied immunohistochemical expression of bcl-2 protein and p53 protein, which are apoptosis-related factors, and cell proliferative activity using Ki-67 antibody. No significant change was noted between apoptotic index and the histological grade of the tumors. In GB, apoptotic cell-rich foci were present at the pseudopalisading necrosis. No correlation between histopathological grades and expression of either p53 or bcl-2 was observed. In GB, however, poor distribution of bcl-2 was found in the areas of pseudopalisade formation. bcl-2 is one of the regulatory factors in the cell cycle and inhibits apoptosis. Expression of apoptosis had no correlation with histopathological grade. However, in GB, the distribution of apoptotic cells showed a correlation with bcl-2-poor foci. It was thought that apoptosis was one of the regulatory factors in the formation of pseudopalisading necrosis in GB.
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PMID:Expression of apoptosis and its related protein in astrocytic tumors. 1053 18

In contrast to primary central nervous system lymphomas (PCNSLs) that occur in immunocompetent patients, most of those that occur in immunosuppressed patients are associated with Epstein-Barr virus (EBV). BCL-2-related proteins either block or promote cell death, forming homo- or heterodimers with each other. LMP-1, EBV latent protein, has been shown to upregulate BCL-2 and BCL-XL. This observation suggests that these proteins may be involved in the transformation process of EBV-infected cells. Twenty-three cases of PCNSLs were studied: 12 of the patients were immunosuppressed, and 11 were immunocompetent. For all cases, we collected clinical information, histologic data, and immunophenotype and tested for the presence of EBV (EBER-1, LMP-1). Apoptosis was assessed by the TdT-mediated dUTP-biotin nick-end labeling method and quantified by image analysis. In three cases, electron microscopy was performed. The BCL-2 family proteins (BCL-2, BCL-X, MCL1, and BAX) and p53 expression were studied by immunohistochemistry on paraffin slides. All cases were classified as diffuse large B-cell lymphomas. PCNSLs in immunosuppressed patients were characterized by EBV association, necrosis, important gliosis, and numerous macrophages. There was no significant difference between the two groups regarding the TdT-mediated dUTP-biotin nick-end labeling staining (P = .08). In contrast, PCNSLs in immunosuppressed patients were shown to express high levels of BCL-2, BCL-X, and BAX in more than 80% of tumor cells in 7, 10, and 11 cases, respectively. In immunocompetent patients, only one case showed a high level of BCL-2 expression in more than 80% of the cells, whereas BCL-X and BAX were overexpressed in two cases. These differences are significant (P < .05). In contrast, there was no significant difference between the two groups in MCL-1 expression. Besides EBV association and necrosis, PCNSLs related to immunosuppression are characterized by an overexpression of BCL-2-related proteins, without dramatically modifying their susceptibility for apoptosis.
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PMID:Overexpression of BCL-2, BCL-X, and BAX in primary central nervous system lymphomas that occur in immunosuppressed patients. 1069 73

Previous studies have shown that lungs of adult mice exposed to >95% oxygen have increased terminal deoxyribonucleotidyltransferase dUTP nick end-label staining and accumulate p53, the expression of which increases in cells exposed to DNA-damaging agents. The present study was designed to determine whether hyperoxia also increased expression of the growth arrest and DNA damage (GADD) gene 45 and GADD153, which are induced by genotoxic stress through p53-dependent and -independent pathways. GADD proteins have been shown to inhibit proliferation and stimulate DNA repair and/or apoptosis. GADD45 and GADD153 mRNAs were not detected in lungs exposed to room air but were detected after 48 and 72 h of exposure to hyperoxia. In situ hybridization and immunohistochemistry revealed that hyperoxia increased GADD45 and GADD153 expression in the bronchiolar epithelium and GADD45 expression predominantly in alveolar cells that were morphologically consistent with type II cells. Hyperoxia also increased GADD expression in p53-deficient mice. Terminal deoxyribonucleotidyltransferase dUTP nick end-label staining of lung cells from p53 wild-type and p53-null mice exposed to hyperoxia for 48 h revealed that hyperoxia-induced DNA fragmentation was not modified by p53 deficiency. These studies are consistent with the hypothesis that hyperoxia-induced DNA fragmentation is associated with the expression of GADD genes that may participate in DNA repair and/or apoptosis.
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PMID:p53-independent induction of GADD45 and GADD153 in mouse lungs exposed to hyperoxia. 1071 May 28

We present the establishment of a natural killer (NK) leukemia cell line, designated KHYG-1, from the blood of a patient with aggressive NK leukemia, which both possessed the same p53 point mutation. The immunophenotype of the primary leukemia cells was CD2+, surface CD3-, cytoplasmic CD3epsilon+, CD7+, CD8alphaalpha+, CD16+, CD56+, CD57+ and HLA-DR+. A new cell line (KHYG-1) was established by culturing peripheral leukemia cells with 100 units of recombinant interleukin (IL)-2. The KHYG-1 cells showed LGL morphology with a large nucleus, coarse chromatin, conspicuous nucleoli, and abundant basophilic cytoplasm with many azurophilic granules. The immunophenotype of KHYG-1 cells was CD1-, CD2+, surface CD3-, cytoplasmic CD3epsilon+, CD7+, CD8alphaalpha+, CD16-, CD25-, CD33+, CD34-, CD56+, CD57-, CD122+, CD132+, and TdT-. Southern blot analysis of these cells revealed a normal germline configuration for the beta, delta, and gamma chains of the T cell receptor and the immunoglobulin heavy-chain genes. Moreover, the KHYG-1 cells displayed NK cell activity and IL-2-dependent proliferation in vitro, suggesting that they are of NK cell origin. Epstein-Barr virus (EBV) DNA was not detected in KHYG-1 cells by Southern blot analysis with a terminal repeat probe from an EBV genome. A point mutation in exon 7 of the p53 gene was detected in the KHYG-1 cells by PCR/SSCP analysis, and direct sequencing revealed the conversion of C to T at nucleotide 877 in codon 248. The primary leukemia cells also carried the same point mutation. Although the precise role of the p53 point mutation in leukemogenesis remains to be clarified, the establishment of an NK leukemia cell line with a p53 point mutation could be valuable in the study of leukemogenesis.
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PMID:A novel natural killer cell line (KHYG-1) from a patient with aggressive natural killer cell leukemia carrying a p53 point mutation. 1080 26

The experiments were designed to study correlation between frequency of apoptosis of Reed-Sternberg/Hodgkin (R-S/H) cells, EBV infection of these cells, expression of the key proteins involved in regulation of apoptosis and cell cycle in R-S/H cells, the patients' pretreatment markers and the clinical outcome. One hundred and ten Hodgkin's disease (HD) patients were studies, of which 69 obtained complete remission (CR) after first-line treatment and 41 did not respond. The time of follow-up was from 18 to 242, median 69.7, months. Apoptosis was evaluated by TUNEL technique (TdT-mediated dUTP nick end labeling) and the presence of EBV-latent membrane protein 1 as well as expression of Bcl-2, tumor suppressor p53, p21WAF1, MDM-2, Rb1, PCNA, p27KIP1 and caspase-3, was detected immunocytochemically on paraffin-embedded lymph node specimens obtained at diagnosis. Positive TUNEL reaction was found in 43 patients with apoptotic index (AI) in this group varying between 10% and 60%. In the remaining 57 patients AI of R-S/H cells was below 10%. In 62 patients the cells surrounding R-S/H cells were also TUNEL-positive; their frequency was variable. The expression of LMP1 protein on R-S/H cells was found in 38 patients, without any correlation with the presence or frequency of apoptosis. No significant difference was seen between the AI and both clinical stage and histological type of the disease. However, the mean AI in non-responding patients was significantly higher than in CR group (p=0.015); the high frequency of apoptosis was also negatively correlated with the progression free survival time (p=0.031) and the overall survival (p=0.042). The expression of PCNA, p21WAF1, p53 protein and caspase-3 also showed positive correlation with frequency of apoptosis (p=0.011, p=0.036, and p=0.001, respectively). On the other hand, no statistically confirmed correlation was found between AI and expression of bcl-2, MDM-2, Rb1, and p27KIP1 on R-S/H cells. These data provide evidence that tumor cells in HD undergo spontaneous apoptosis regardless of EBV infection. High pretreatment AI correlates with poor response to the treatment, and may be considered as a potential negative prognostic factor in HD.
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PMID:Spontaneous apoptosis of Reed-Sternberg and Hodgkin cells; clinical and pathological implications in patients with Hodgkin's disease. 1093 5

The oncoproteins Bcl-2 and Bax, the tumor suppressor gene product p53, TUNEL (TdT [terminal deoxynucleotidyl transferase] dUTP nick end-labeling) and the cell-cycle antigen Ki-67 were studied in 71 cases of mucoepidermoid carcinoma originating in the oral minor salivary glands. Grade I tumors had higher expression of Bcl-2 than Grade II and III tumors (chi2 test, 0.01<P<0.025) and the Bcl-2-positive group had a higher survival rate than the Bcl-2-negative group (generalized Wilcoxon, P = 0.00051). Patients with strong TUNEL positivity had a higher survival rate than those with either weak positivity or negativity (generalized Wilcoxon, P = 0.047). The expression of p53 and TUNEL had a positive correlation (P = 0.0315). Grade II and III tumors had a higher frequency of positive Ki-67 expression than Grade I tumors (chi2 test, 0.01<P<0.025) and patients with Ki-67-negative tumors had better survival than patients with Ki-67-positive tumors (generalized Wilcoxon, P = 0.000099). This study showed that Bcl-2 proteins, p53 protein, TUNEL and Ki-67 are potentially useful prognostic markers for survival in patients with mucoepidermoid carcinoma of the oral minor salivary glands.
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PMID:Apoptosis and apoptotic-related factors in mucoepidermoid carcinoma of the oral minor salivary glands. 1097 57

The present study was carried out to elucidate the relationship between cancer cell growth and apoptosis in morphogenesis of colorectal cancer, and the role of p53 expression, one of apoptosis-related genes, in apoptosis. Specimens from 82 cases of colorectal cancer, all surgically resected, were divided into intramucosal polypoid growth (PG) and nonpolypoid growth (NPG) types according to Shimoda's classification. Expressions of proliferating cell nuclear antigen (PCNA) and p53 protein were assessed by immunohistochemical staining, and apoptosis by the TdT-mediated dUTP-biotin nick end labeling (TUNEL) method. Immunohistological detection of p53 protein was performed by the use of Pab1801. In the assessment of PCNA and apoptosis the numbers of positive cells per 1000 tumor cells were expressed as PCNA labeling index (L.I.) and apoptosis labeling index (Apo L.I.), respectively. In tumor invading muscularis propria (mp), the cancer tumor tissue was equally divided into three by the depth, top, middle, and bottom, and the number of apoptosis-positive cells per 500 tumor cells was calculated per each depth of invasion and compared between PG and NPG types. PCNA L.I. was 658.5 +/- 127.1 (mean +/- SD) in PG type. When determined according to depth of invasion, PCNA L.I. was 533.8 +/- 188.2 for tumor invading submucosa (sm), 741.8 +/- 62.2 for mp, and 679.2 +/- 94.3 for tumor invading subserosa or penetrating the serosa (ss-a). The corresponding values in the NPG type were 651.9 +/- 176.2, 482.2 +/- 227.1, 766.2 +/- 90.7, and 690.9 +/- 84.3, respectively. There was no significant difference in the relationship of PCNA L.I. with the depth of invasion in both growth types. Apo L.I. was 19.9 +/- 9.8 in PG type. When determined according to depth of invasion, Apo L.I. was 29.2 +/- 9.7 for sm, 21.7 +/- 9.0 for mp, and 15.4 +/- 7.0 for ss-a. The corresponding values in the NPG type were 52.8 +/- 25.1, 67.5 +/- 25.6, 37.2 +/- 9.4, and 52.6 +/- 26.3, respectively. Apo L.I. of NPG type was significantly higher than that of PG type in each depth of invasion (p < 0.01). In mp tumor the numbers of apoptosis-positive cells in the top, middle, and bottom of the PG type were 8.0 +/- 4.8, 11.8 +/- 3.9, and 12.9 +/- 5.9, and the corresponding values of the NPG type were 26.6 +/- 7.6, 17.3 +/- 5.3, and 11.8 +/- 4.3, respectively. The number of apoptosis in the top and middle of the lesion of NPG tumors was significantly higher than that of PG tumors. There was no difference in the number of apoptosis in the bottom of the lesion between the NPG and the PG types. There was no significant difference in the Apo L.I. between p53 positive cancers and negative cancers. These results indicate that colorectal cancers show a pattern of PG if apoptosis is low, and a pattern of NPG if apoptosis is high, and that apoptosis of colorectal cancer cell is not regulated by p53.
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PMID:[Significance of cancer cell growth and apoptosis in morphogenesis of colorectal cancer]. 1107 Jul 93

Ultraviolet radiation can induce the injury of epidermal keratinocytes, resulting in sunburn cell (apoptotic cell) formation. It has been demonstrated that the protease caspase-3, a downstream molecule of the CD95 pathway, is activated in UV-exposed HaCaT cells, and that the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is cleaved by interleukin-1beta converting enzyme (ICE)-like protease during apoptosis induced by X-rays, staurosporine and etoposide. Then, we studied whether the DNA-PKcs is cleaved during UV-induced apoptosis in keratinocytes. We used the well-characterized cloned human keratinocyte cell line HaCaT, which carries p53 mutations. UVB-induced apoptotic cells were observed by TdT-mediated deoxyuridine 5'-triphosphate nick end labeling (TUNEL) assay and agarose gel electrophoresis. Western blot analysis was performed using the antibody against DNA-PKcs. The cleavage occurred during UVB-induced apoptosis in HaCaT cells. It suggests that the cleavage is associated with loss of DNA-PK activity. Thus, a functional relevance of cleavage of DNA-PKcs may be to prevent rejoining fragmented DNA during apoptosis, thereby promoting apoptotic processes. Although apoptosis was not completely blocked by the caspase-3 inhibitor, the cleavage of the DNA-PKcs was blocked. These results indicate that DNA-PKcs is cleaved by the caspase-3 for UVB-induced apoptosis in HaCaT cells.
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PMID:DNA-dependent protein kinase catalytic subunit is cleaved during UV-induced apoptosis. 1115 67


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