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)

The p53 tumor suppressor is activated in response to a variety of cellular stress signals, although specific in vivo signals that trigger tumor suppression are unknown. In mouse thymocytes, where p53 inactivation leads to tumorigenesis, several observations suggest that V(D)J recombination of T-cell receptor (TCR) loci could provide a DNA damage signal triggering p53-dependent apoptosis and tumor suppression. Inactivation of p53 would allow V(D)J driven mutation of additional cancer genes, facilitating tumorigenesis. Here, we show that mice with a p53 deficiency in thymocytes and unable to carry out V(D)J recombination are not impaired in the development of thymoma. Recombination-activating gene (RAG) deficiencies were introduced into both p53-/- mice and TgTDeltaN transgenic mice, a strain in which 100% of the mice develop thymoma due to thymocyte-specific inactivation of p53 by a simian virus 40 T-antigen variant. V(D)J recombination was dispensable for tumorigenesis since thymomas developed with or without the RAG-1 or RAG-2 gene, although some delay was observed. When V(D)J recombination was suppressed by expression of rearranged TCR transgenes, 100% of the TgTDeltaN mice developed thymoma, surprisingly with reduced latency. Further introduction of a RAG deficiency into these mice had no impact on the timing or frequency of tumorigenesis. Finally, karyotype and chromosome painting analyses showed no evidence for TCR gene translocations in p53-deficient thymomas, although abundant aneuploidy involving frequent duplication of certain chromosomes was present. Thus, contrary to the current hypothesis, these studies indicate that signals other than V(D)J recombination promote p53 tumor suppression in thymocytes and that the mechanism of tumorigenesis is distinct from TCR translocation oncogene activation.
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PMID:No requirement for V(D)J recombination in p53-deficient thymic lymphoma. 958 89

3SB, a mouse thymoma cell line, is one of the most radio-sensitive cells (D0 = 0.3 Gy), and its rapid apoptosis (4 h after 5 Gy irradiation, 90% apoptosis) seems to play a decisive role in enhancing the radiosensitivity. To understand the molecular mechanisms underlying extremely high radiosensitivity and rapid apoptosis, we attempted to isolate X-ray-resistant (XR) variants from 3SBH5, a stable subclone of 3SB, by repeating exposure of the cells to 2-5 Gy X-rays. Four independent stable XR variants, R111, R223, R316 and R429, were isolated by the repeated irradiation protocols. All XR cells possessed about 3 times higher D10 values than that of their parental 3SBH5. They were also resistant to apoptosis; only 10% cells underwent apoptosis 4 h after 5 Gy irradiation. The p53 protein was induced in all the cell lines after 5 Gy X-irradiation. These variants showed a cross resistance to a chemical reagent daunorubicin (DNR) that is known to be involved in the ceramide-mediated apoptosis. DNR, as well as C2-ceramide (5 muM) induced apoptosis in parental 3SBH5 cell, but not in two XR variants, R233 and R316 cells. Present result suggests that the induction of X-ray resistance by repeated X-irradiation might be achieved, at least partly, by the enhanced resistance to the ceramide-mediated apoptosis.
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PMID:Radio-sensitive murine thymoma cell line 3SB: characterization of its apoptosis-resistant variants induced by repeated X-irradiation. 972 9

Thymic carcinoma is an uncommon tumor. Most cases appear to arise de novo, but in rare instances they can arise in thymomas. We report the clinicopathologic features and immunohistochemical profile of five cases of thymic carcinoma accompanied by a component of thymoma. Immunohistochemical studies were performed with the avidin-biotin-peroxidase complex method using monoclonal antibodies to p53(DO7), CD99(O13), epithelial membrane antigen, CD5(NCL-CD5-4C7), vimentin (V9), and cytokeratins 7, 8, 18, and 19. The patients consisted of three men and two women with a median age of 57 years. One patient had myasthenia gravis, and the other four presented with chest symptoms. One patient had concurrent adenocarcinoma of the lung with metastasis. Four of the patients died within 15 months. The thymomas consisted of two large polygonal cell thymomas, two squamoid thymomas, and one spindle cell thymoma. The malignant components included two undifferentiated carcinomas, one spindle cell carcinoma, one squamous cell carcinoma, and one clear cell carcinoma with squamous differentiation. There was no correlation between the histologic types of the thymoma and the thymic carcinoma. In three cases, excluding the two squamoid thymomas, the thymic carcinomas occurred in the necrotic areas of the thymoma. They showed upregulated expression of epithelial membrane antigen and cytokeratins 7, 8, 18, and 19, similar to the so-called "interface phenomenon" described in the invasion front of other types of carcinoma. Increased p53 protein expression was observed in all five carcinomas, and there was loss of CD99+ immature T lymphocytes. Among the thymic carcinomas, only the squamous component of the clear-cell carcinoma stained for CD5, a marker commonly expressed in thymic carcinomas. Paradoxically, a squamoid thymoma, but not its associated spindle cell carcinoma, expressed CD5, suggesting the acquisition of an "aggressive" phenotype by the squamoid thymoma, but with loss of the marker on malignant transformation. One undifferentiated carcinoma acquired vimentin immunoreactivity, whereas four other carcinomas and all five thymomas were negative. In conclusion, thymic carcinoma can arise in any histologic type of thymoma, including spindle cell thymoma, which is generally regarded as a benign neoplasm. The prognosis appears to be poor. Tumor necrosis in a thymoma should alert the pathologist to search for malignant change. The malignant change is commonly associated with increased expression of epithelial membrane antigen, cytokeratin subtypes, or p53 protein, and loss of CD99+ immature T lymphocytes, and is occasionally associated with a change in the expression of CD5 or vimentin.
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PMID:Thymic carcinoma arising in thymoma is associated with alterations in immunohistochemical profile. 985 Jan 73

We examined p53 protein expression, p53 gene mutation, proliferating cell nuclear antigen (PCNA), and argyrophilic nuclear organizer regions (AgNOR), in 30 patients with surgically-treated thymic tumors (26 thymoma and 4 thymic carcinoma cases). p53 expression ratio with DO-1 was divided as p53 negative (0% positivity), low expressor (<10% positivity), high expressor (>10% positivity). The incidence of p53 low and high expressor in thymoma were 19% (5/26) and 8% (2/26), respectively. p53 immunopositivity in thymoma was significantly correlated with PCNA labeling index (LI). p53 expression ratio in invasive thymoma (33%) tended to be higher than that in non-invasive thymoma (18%). p53 expression was detected in one of the thymic carcinoma. There were no p53 gene mutations in 15 invasive thymoma, although one of four (25%) thymic carcinomas showed two point mutations. p53 gene alterations seem to be associated with malignant activity of tumor cells, and therefore detection of p53 gene mutations is useful as a diagnostic factor.
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PMID:p53 alteration, proliferating cell nuclear antigen, and nucleolar organizer regions in thymic epithelial tumors. 985 2

Aggregates of benign nevus cells occurring in lymph nodes are a well-described incidental finding. Nevus cell aggregates (NCAs) can mimic foci of metastatic carcinoma or other disease processes, so the surgical pathologist should be familiar with this lesion. The purpose of this report is to describe the potential diagnostic difficulties created by benign NCAs within the thymus of a 32-year-old man with dysplastic nevus syndrome and malignant melanoma involving mediastinal lymph nodes and the right lung. Morphologically, the NCAs in this case elicited the differential diagnoses of metastatic melanoma and thymoma. Immunohistochemical studies helped to establish the correct diagnosis by demonstrating reactivity for S-100 protein and negative staining for keratin and HMB-45. Unlike malignant melanomas, NCAs show no p53 protein immunoreactivity, and low proliferative activity was detected by Ki-67 antigen immunostaining. Although melanocytic cells were rarely reported in thymic neoplasms, we are not aware of any previous reports of NCAs occurring in the normal thymus.
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PMID:Benign nevus cell aggregates in the thymus: a case report. 1010 20

Chromosome translocations involving T cell receptor (TCR) loci have been found in tumors from Ataxia telangiectasia (AT) patients and in mouse Atm-/- thymoma, suggesting the involvement of V(D)J recombination in these malignancies. By introducing a RAG-1 deficiency into Atm-/- mice in the presence of a TCR transgene, we show that V(D)J recombination is critical for thymoma development in these mice. Therefore, aberrant V(D)J recombination, normally suppressed by Atm, facilitates tumorigenic events leading to cancer. Because V(D)J recombination is dispensable for lymphomagenesis upon p53 deficiency, this study also indicates that Atm and p53 function by distinct mechanisms in suppressing thymoma.
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PMID:Critical role for Atm in suppressing V(D)J recombination-driven thymic lymphoma. 1034 13

We review cases of thymic cell tumor treated between January 1991 and March 1998. Nineteen of the 23 cases studied involved thymoma. Eight (42%) were asymptomatic, 4 (21%) were associated with myasthenia gravis and 7 (37%) were symptomatic. The most common symptom was non-specific chest pain, reported by 4 (47%) patients with symptoms. Classifying the cases of thymoma by Masaoka's system, we found that 12 were cases of thymoma in stage I (63.2%), 4 in stage II (21.1%) and 3 in stage III (15.8%). No stage IV patients were treated. Treatment consisted of full exeresis of the tumor in 17 (89.5%) cases, partial resection in one case (5.2%) and biopsy of the tumor in one non-resectable, case. Adjuvant radiotherapy was applied in seven cases. Chemotherapy was not prescribed. With follow-up ranging from 9 to 96 months, half the patients survived 21 months after surgery. Among the surviving patients, mortality was nil at the end of the study. The results of microscopic, cytologic and blood analyses were of scarce value in differentiating between benign and malignant tumors, even though p53 and bcl2 antigen positivity and clinical stage have been related to poor prognosis in recent years.
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PMID:[Thymoma. A retrospective study]. 1043 29

It is impossible to predict malignant potential of thymomas by conventional histopathological examination. In order to find a malignant marker of thymoma, we immunohistochemically examined the expression of the products of p53 and p27kip1, potential tumor suppressor genes in thymic epithelial tumors. The thymic epithelial tumors examined in the present study included 13 non-invasive thymomas, 7 invasive thymomas, and 4 thymic carcinomas. The thymic epithelial cells showed abnormal accumulation of p53 protein in 2 of 13 non-invasive thymomas (15.4%), 4 of 7 invasive thymomas (50%), and 3 of 4 thymic carcinomas (75%). The frequency of p53-expression paralleled with clinical aggressiveness. On the other hand, p27 showed no correlation with clinical aggressiveness. In conclusion, the present results suggest that the presence of p53-positive epithelial cells might be a useful indicator to predict malignant potential of thymoma.
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PMID:[Correlation between clinical aggressiveness of thymic epithelial tumors and expression of tumor suppressor gene products (p53, p27)]. 1049 46

The involvement of the tumor suppressor protein, p53, in thymic epithelial cell-induced apoptosis of CD4+8+ (double positive) thymocytes, was studied in an in vitro model consisting of a thymic epithelial cell line (TEC) and thymocytes. p53 expression was not augmented in double positive (DP) thymocytes upon co-culturing with TEC, although extensive apoptosis was observed. In the same cells, p53 expression was upregulated in response to low ionizing irradiation, which was accompanied with massive apoptosis. Moreover, TEC induced apoptosis in two DP thymomas, derived from p53(-/-) mice, and in a double positive thymoma clone expressing mutant p53. The extent and kinetics of TEC-induced apoptosis was not affected by the status of p53 in the thymocytes tested. We conclude that thymic epithelial cell-induced apoptosis of immature DP thymocytes is p53-independent and apparently, involves a different apoptotic pathway than that triggered by DNA damage.
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PMID:p53 and thymic 'death by neglect': thymic epithelial cell-induced apoptosis of CD4+8+ thymocytes is p53-independent. 1074 69

The classification of thymic epithelial tumors is controversial because prediction of the biological behavior of these tumors from their morphologic appearance is difficult. The aim of this study was to evaluate the proliferative activity and rate of apoptosis of thymic epithelial tumors classified according to World Health Organization histological classification. We also attempted to determine the importance of a number of proapoptotic factors in these processes. We investigated 46 surgically resected thymic epithelial tumors (8 Type A, 8 Type AB, 7 Type B1, 7 Type B2, 6 Type B3, and 10 Type C). Immunohistochemical staining was performed to determine the tumor expression of p53 protein, Bax, Bcl-2, and survivin. In addition, the Ki-67 labeling index (LI) and apoptotic index (AI) of these tumors were evaluated. Type C thymoma had a higher LI (16.55 +/- 12.12%) than did the other histological subtypes. Stage IV thymoma (12.36 +/- 9.99%) had a higher LI than did Stage I tumor. The AI was significantly elevated in Type B1 thymoma (1.47 +/- 0.55%). Overexpression of p53 protein was observed in Type B3 and C thymomas. p53 protein-positive tumors had a higher LI than did p53 protein-negative tumors (P <.0001). Bcl-2 expression was observed in Type A, AB, and C thymomas. Bcl-2-positive thymoma had a lower AI than did Bcl-2-negative thymoma (P =.0157). These results suggest that overexpression of p53 protein is associated with a higher tumor proliferative activity and that Bcl-2 acts as an inhibitor of apoptosis in thymoma. Bcl-2 and p53 protein expression may be useful markers in differentiating thymoma subtypes.
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PMID:Proliferative activity and apoptosis in thymic epithelial neoplasms. 1248 Oct 14


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