Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Functional regulation of p53 protein, a critical regulator of cell cycle and apoptosis, was investigated in fiberoptic bronchoscopy biopsy samples taken from 23 patients suffering from recurrent squamous cell lung cancer by analyzing the expression and phosphorylation status of the p53 at Ser15 and Ser20 before and after treatment with radiotherapy/cisplatin/vinorelbine. Poly(ADP-ribose) levels as a marker of cellular DNA damage, expression of wild-type and mutated p53 protein, and Ki-67 expression as a marker of proliferation was also determined. Median p53 expression increased (61% increase) after therapy. p53 phosphorylated on Ser20 was also increased by approximately 57% in radiotherapy/chemotherapy patients, and these changes correlated with Ki-67 proliferation and with elevated (by 69%; P < 0.01) poly(ADP-ribose) levels. Our data indicate that apart from changes in p53 quantity, post-translational phosphorylation/dephosphorylation-mediated alterations, especially at Ser20 may play a role in p53 stabilization and, therefore, in antiproliferative activity of drugs inducing DNA damage and apoptosis.
Am J Respir Cell Mol Biol 2004 Apr
PMID:p53 N-terminal Ser-15 approximately P and Ser-20 approximately P levels in squamous cell lung cancer after radio/chemotherapy. 1452 25

Laminin is a basement membrane glycoprotein implicated in a large number of biologic activities of cancer progression, many of which are mediated by the presence of the laminin receptor (67LR) on the cell membrane. We studied the correlations of laminin and its receptor with standardized and new prognostic factors (including bone marrow micrometastases) in a series of 112 patients with operable breast cancers. Laminin-positive cells were detected in 60% of the tumors and 67LR-positive cells in 55%; both were present in 35% of the cases. No association was found between laminin or 67LR positivity and pathologic tumor size, pathologic nodal status, grading, Ki-67, estrogen receptor status, progesterone receptor status, or bone marrow micrometastases. The only statistically significant association was with menopausal status and age, with a higher percentage of 67LR-positive tumors among premenopausal and younger patients. The median follow-up was approximately 7 years. The prognosis of disease-free survival was similar in the laminin-positive and laminin-negative subjects but was significantly better in 67LR-negative patients; there were no significant differences in overall survival. The prognostic role of laminin and 67LR in disease-free survival and overall survival varied according to nodal status. In the absence of nodal involvement, the risk of relapse (and death) was greater in the patients who were positive for laminin, 67LR, or both than in those who were negative for laminin, 67LR, or both; in the case of 4 or more involved nodes, the prognostic role of laminin and 67LR was reversed. These results did not change after adjustment for age, menopausal status, tumor status, nodal status, grading, or bone marrow micrometastases.
Appl Immunohistochem Mol Morphol 2003 Dec
PMID:Prognostic significance of laminin, laminin receptor, and bone marrow micrometastases in breast cancer patients: are these markers of aggressive behavior and metastatic potential? 1466 56

We here show that the early postmitotic stage of granule cell development during adult hippocampal neurogenesis is characterized by the transient expression of calretinin (CR). CR expression was detected as early as 1 day after labeling dividing cells with bromodeoxyuridine (BrdU), but not before. Staining for Ki-67 confirmed that no CR-expressing cells were in cell cycle. Early after BrdU, CR colocalized with immature neuronal marker doublecortin; and later with persisting neuronal marker NeuN. BrdU/CR-labeled cells were negative for GABA and GABAA1 receptor, but early on expressed granule cell marker Prox-1. After 6 weeks, no new neurons expressed CR, but all contained calbindin. Stimuli inducing adult neurogenesis have limited (enriched environment), strong (voluntary wheel running), and very strong effects on cell proliferation (kainate-induced seizures). In these models the induction of cell proliferation was paralleled by an increase of CR-positive cells, indicating the stimulus-dependent progression from cell division to a postmitotic stage.
Mol Cell Neurosci 2003 Nov
PMID:Transient calretinin expression defines early postmitotic step of neuronal differentiation in adult hippocampal neurogenesis of mice. 1466 11

It has recently become clear that the nucleolus, the most prominent nuclear subcompartment, harbors diverse functions beyond its classic role in ribosome biogenesis. To gain insight into nucleolar functions, we have purified amplified nucleoli from Xenopus laevis oocytes using a novel approach involving fluorescence-activated cell sorting techniques. The resulting protein fraction was analyzed by mass spectrometry and used for the generation of monoclonal antibodies directed against nucleolar components. Here, we report the identification and molecular characterization of a novel, ubiquitous protein, which in most cell types appears to be a constitutive nucleolar component. Immunolocalization studies have revealed that this protein, termed NO66, is highly conserved during evolution and shows in most cells analyzed a dual localization pattern, i.e., a strong enrichment in the granular part of nucleoli and in distinct nucleoplasmic entities. Colocalizations with proteins Ki-67, HP1alpha, and PCNA, respectively, have further shown that the staining pattern of NO66 overlaps with certain clusters of late replicating chromatin. Biochemical experiments have revealed that protein NO66 cofractionates with large preribosomal particles but is absent from cytoplasmic ribosomes. We propose that in addition to its role in ribosome biogenesis protein NO66 has functions in the replication or remodeling of certain heterochromatic regions.
Mol Biol Cell 2004 Apr
PMID:NO66, a highly conserved dual location protein in the nucleolus and in a special type of synchronously replicating chromatin. 1474 13

We examined the effects of interferon-alpha (IFN-alpha) treatment on the growth, cell cycle, proliferation, and apoptotic parameters as well as adhesive properties and proteome of chronic myelogenous leukemia (CML)-derived K562 cells. IFN-alpha treatment (200 to 600 U/ml, 24 to 72 h) suppressed growth and caused accumulation of K562 cells in the S-phase of cell cycle (increase in S-phase cells by up to 52% in comparison with the untreated controls) at the expenses of cells in G1-phase. No transition of cells to G0-phase occurred as followed from Ki-67 protein determination. Although the level of chimeric gene product, BCR-ABL mRNA coding for BCR-ABL protein with anti-apoptotic properties, decreased by 30%, apoptosis was not triggered as judged from Annexin-V, APO2.7, and TUNEL assays. Adhesion of K562 cells to fibronectin-coated surfaces increased by up to 52% as determined by calcein assay. The proteomic analysis (2-D electrophoresis in combination with mass spectrometry, MALDI-MS) revealed a single protein, ubiquitine cross-reactive protein (UBCR), whose level markedly increased due to IFN-alpha treatment. The ubiquitination-like directed degradation processes may thus play a role in the mechanism of IFN-alpha antiproliferative effects.
Blood Cells Mol Dis
PMID:Interferon-alpha suppresses proliferation of chronic myelogenous leukemia cells K562 by extending cell cycle S-phase without inducing apoptosis. 1475 43

We have reported that interleukin-1 beta (IL-1 beta) upregulates cardiac expression of vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR-2), raising the possibility that IL-1 beta plays an important role in VEGF-mediated neovascularization. In this study, we examined the cellular mechanism for ischemia-induced neovascularization using IL-1 beta knock-out (-/-) mice. Recovery of blood perfusion in ischemic hindlimb in IL-1 beta-/- mice was markedly (43% decrease) impaired as compared with the wild-type mice. CD31(+) vessel numbers and Ki-67(+) neo-capillaries were significantly (P < 0.01) decreased 44% and 68%, respectively. IL-1 beta expression was localized in the capillary vessels in ischemic limb muscles. Ischemia-induced expressions of hypoxia-inducible factor 1 alpha (HIF-1 alpha), VEGF, its receptor VEGFR-2 and vascular cell adhesion molecule-1 (VCAM-1) were markedly inhibited in the IL-1 beta-/- mice. Hindlimb ischemia-induced an increase (1.22% out of total nuclear cell) in CD34(-)/B220(-)/CD3(-)/Flk-1(+) hematopoietic stem cell population in peripheral blood in the wild-type mice, whereas in the IL-1 beta-/- mice such increase was only 0.09%. Injection of IL-1 beta protein into the wild-type mice markedly increased the ratio of the CD34(-)/B220(-)/CD3(-)/Flk-1(+) cell population (from 0.03% to 0.7%) in the peripheral blood associated with an increase in the number of endothelial cells. Such IL-1 beta-mediated increases in cell numbers were blocked by co-injection of anti-VEGF antibody. CD34(-)/B220(-)CD3(-)Flk-1(+) cells trans-differentiated into eNOS- and CD31-expressing endothelial cells in vivo and in vitro. This study demonstrates that IL-1 beta plays a key role in ischemia-induced neovascularization by mobilizing CD34(-)/B220(-)CD3(-)Flk-1(+) endothelial precursor cells in a VEGF-dependent manner as well as by upregulating expressions of VEGF, VEGFR-2 and adhesion molecules on endothelial cells.
J Mol Cell Cardiol 2004 Apr
PMID:Mechanism for IL-1 beta-mediated neovascularization unmasked by IL-1 beta knock-out mice. 1508 5

We examined the immunohistochemical expression of aromatase cytochrome P450 (P450arom), estrogen receptor (ER), progesterone receptor (PR), and Ki-67 in postoperative uterine sarcomas (n = 31) and the corresponding eutopic endometria (n = 20) to evaluate the relationships between the endocrine character of uterine sarcomas and the clinical features. In sarcoma tissues, P450arom was detected in 55% of cases, ER in 42%, PR in 42%, and Ki-67 in 90%. In eutopic endometria, P450arom was detected in 60% of cases, ER in 60%, and PR in 35%. There were correlations in the steroid-related proteins between the tumors and endometria (P = 0.001-0.026). The positivity of endometrial P450arom (P = 0.04) and ER (P = 0.006) was higher in surviving patients than dead patients regardless of the menstrual state. The results demonstrate correlation between the expression of P450arom, ER, and PR in tumors and eutopic endometria. Intense expression of the steroid-related proteins was associated with better survival.
J Steroid Biochem Mol Biol 2004 Feb
PMID:Aromatase cytochrome P450 and estrogen and progesterone receptors in uterine sarcomas: correlation with clinical parameters. 1508 50

Dividing cardiomyocytes are observed in autopsied human hearts following recent myocardial infarction, however there is a lack of information in the literature on the division of these cells. In this study we used a rat model to investigate how and when adult mammalian cardiomyocytes proliferate by cell division after myocardial infarction. Myocardial infarction was induced in Wistar rats by ligation of the left coronary artery. The rats were sacrificed periodically up to 28 days following induced myocardial infarction, and the hearts subjected to microscopic investigation. Cardiomyocytes entering the cell cycle were assayed by observation of nuclear morphology and measuring expression of Ki-67, a proliferating cell marker. Ki-67 positive cardiomyocytes and dividing nuclei were observed initially after 1 day. After 2 days dividing cells gradually increased in number at the ischemic border zone, reaching a peak increase of 1.12% after 3 days, then gradually decreasing in number. Dividing nuclei increased at the ischemic border zone after 3 days, peaked by 0.14% at day 5, and then decreased. In contrast, Ki-67 positive cells and dividing nuclei were limited in number in the non-ischemic area throughout all experiments. In conclusion, mitogenic cardiomyocytes are present in the adult rat heart following myocardial infarction, but were spatially and temporally restricted.
Mol Cell Biochem 2004 Apr
PMID:Cardiomyocytes undergo cells division following myocardial infarction is a spatially and temporally restricted event in rats. 1512 22

We report a new case of synovial sarcoma of the kidney. The patient underwent nephrectomy because of a large tumor in the right kidney. The histologic diagnosis was hemangiopericytoma. Less than 1 year after primary surgery the patient was reoperated due to massive local recurrence. Histology now revealed a poorly differentiated tumor tissue with hemangiopericytoma-like features. Immunostainings showed immunoreactivity to cytokeratin, epithelial membrane antigen, and vimentin. The tumor was negative to CD34 and factor VIII. The tumor cell proliferation, assessed by Ki-67, was high. RT-PCR analysis and sequence analysis demonstrated the presence of SS18/SSX2 fusion gene. Review of the histologic specimens from the original tumors confirmed hemangiopericytoma-like morphology. The new diagnosis was poorly differentiated synovial sarcoma. At the time of reoperation, lung metastases were detected radiologically, reflecting a very aggressive phenotype. To our knowledge, this is the third case of poorly differentiated synovial sarcoma of the kidney. Common for all these three cases is the hemangiopericytoma-like histology and a very aggressive clinical behavior. These circumstances accentuate the impact of SS18/SSX analysis in diagnosis of renal hemangiopericytoma-like tumors.
Diagn Mol Pathol 2004 Mar
PMID:A novel case of synovial sarcoma of the kidney: impact of SS18/SSX analysis of renal hemangiopericytoma-like tumors. 1516 9

The c-erbB-2 and cyclooxygenase (COX) pathways are involved in the pathogenesis of colorectal carcinoma, but the relationship is not fully understood. This study evaluated the significance of c-erbB-2, COX-2, and Ki-67 protein expression in 185 patients with colorectal carcinoma using tissue microarrays. Only one case expressed cerbB-2 protein. COX-2 expression was noted in 166 of 176 cases (94.3%), and the Ki-67 expression rate averaged 5.9%. There was no relationship among c-erbB-2, COX-2, and Ki-67 protein expression, and COX-2 protein expression was not related to tumor stage, differentiation, size, depth of invasion, lymphatic or vascular invasion, or patient survival. While the contribution of c-erbB-2 to colorectal carcinogenesis may be of little quantity, COX-2 may be deeply involved in colorectal carcinogenesis.
Appl Immunohistochem Mol Morphol 2004 Mar
PMID:Cyclooxygenase-2 and c-erbB-2 expression in colorectal carcinoma assessed using tissue microarrays. 1516 22


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