Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report the immunological characterization of three colon carcinoma cell lines, COLO 205, SW620 and SW403, which we selected to combine with cytokine-secreting fibroblasts for the development of an allogeneic tumour cell vaccine. The cell lines expressed HLA-A2 as well as shared tumour-associated antigens (TAAs) representative of colon carcinomas: CEA, Ep-CAM, MUC1, HER2/neu and MAGE antigens. They did not secrete high levels of the immunosuppressive factors TGF-beta, IL-10 or prostaglandins. The lines presented TAAs in a manner recognized by immune effector cells, which was demonstrated by the lysis of SW620 by HLA-A2-restricted anti-p53 cytotoxic T lymphocytes (CTL). COLO 205 and SW620 were genetically modified to express the co-stimulatory molecule CD80 (B7.1), which increased the ability of the cells to stimulate CTL in vitro. CTL clones derived from HLA-A2+ peripheral blood mononuclear cells stimulated with the CD80-expressing lines lysed the stimulator cell and an HLA-A2+ colon cancer cell line, but did not lyse an isogeneic fibroblast line or an HLA-A2- colon cancer cell line. CTL clones derived from colon carcinoma patients immunized with an allogeneic vaccine containing these lines demonstrated killing of autologous tumour cells, the vaccine cell lines and other HLA-A2+ colon cancer cell lines, but not fibroblasts isogeneic to certain of the target cell lines. Our studies demonstrate that these colon carcinoma cell lines express shared TAAs that can induce CTLs which recognize and lyse other colon carcinoma cells, and support the continued clinical evaluation of the CD80 gene modified allogeneic colon cell/cytokine-secreting fibroblast carcinoma vaccine.
...
PMID:Antigenic and immunologic characterization of an allogeneic colon carcinoma vaccine. 1210 28

MUC1 and MUC4 are the two membrane mucins that have been best characterized. Although they have superficially similar structures and have both been shown to provide steric protection of epithelial surfaces, recent studies have also implicated them in cellular signaling. They act by substantially different mechanisms, MUC4 as a receptor ligand and MUC1 as a docking protein for signaling molecules. MUC4 is a novel intramembrane ligand for the receptor tyrosine kinase ErbB2/HER2/Neu, triggering a specific phosphorylation of the ErbB2 in the absence of other ErbB ligands and potentiating phosphorylation and signaling through the ErbB2/ErbB3 heterodimeric receptor complex formed in the presence of neuregulin. In contrast, MUC1 has a highly conserved cytoplasmic tail, which binds beta-catenin, a key component of adherens junctions and a regulator of transcription, in a process that is tightly regulated by MUC1 phosphorylation. The specific localization of these membrane mucins to the apical surfaces of epithelial cells suggests that their signaling functions may be important as sensor mechanisms in response to invasion or damage of epithelia.
...
PMID:Cell signaling through membrane mucins. 1250 84

Thirty HLA-A2 women with metastatic breast cancer received up to 14 vaccinations with MDA-MB-231-CD80, an HLA-A2 allogeneic breast cancer cell line, which had been lipofected with the cDNA for the CD80 costimulatory molecule. Tumor cells were administered with BCG or GM-CSF as an adjuvant. Sera obtained before and after vaccination were analyzed for antibodies to tumor cell lysate, MUC1, HER2/neu and p53. Since the cell line was grown in fetal bovine serum (FBS), sera were also analyzed for antibodies to FBS. Eighteen of 24 patients for whom sera were available exhibited anti-FBS activity at baseline. Eleven of these 18 patients and all six patients without baseline anti-FBS activity showed an increased titer after vaccination. The anti-FBS activity required that serum samples be absorbed in excess FBS to detect specific antibodies to tumor cell lysate. A two-fold increase in the titer of IgG specific to tumor cell lysate was observed in 6 patients. Eight of 24 patients made an antibody response to HER-2/neu, four of 24 to MUC1 and one of 24 to p53. Although antibody production to a variety of tumor cell-associated antigens was detected our results suggest that a whole cell vaccine comprising a CD80-transfected allogeneic breast cancer cell line with adjuvant BCG or GM-CSF was not a reliable method to induce significant antibody responses in women with advanced breast cancer.
...
PMID:Identification of tumor-specific antibodies in patients with breast cancer vaccinated with gene-modified allogeneic tumor cells. 1261 8

MUC1 is a tumor antigen, overexpressed in approximately 90% of human breast cancers. In normal glandular epithelia, MUC1 is expressed at the apical surface; however, in carcinomas an aberrantly glycosylated form of MUC1 is upregulated and expressed around the entire surface of the cell. Previously, we have shown that a lack of Muc1 significantly delays tumor progression and/or onset in MMTV-PyV-mT and MMTV-Wnt-1 transgenic mice. Here we show that, unlike the models mentioned above, a loss of Muc1 in MMTV-c-Neu mice (MMTV-c-Neu/Muc1(-/-)) altered neither mammary tumor onset nor progression. Moreover, characterization of MMTV-c-Neu/Muc1(+/+) tumors revealed that Muc1 expression was repressed at the level of transcription. In contrast, normal mammary gland tissue adjacent to tumor tissue expressed Muc1 and pregnant mammary glands from c-Neu transgenic animals expressed high levels of Muc1. We found that transient transfection of activated ErbB2 into human embryonic kidney 293/MUC1 cells resulted in the repression of MUC1 expression. Further, transient transfection of activated ErbB2 resulted in the inhibition of Muc1 transcriptional activation in luciferase reporter assays. These data suggest that the activation of ErbB2, which only occurs in c-Neu tumors, selectively inhibits Muc1 expression.
...
PMID:Downregulation of Muc1 in MMTV-c-Neu tumors. 1473 4

Human CA125, encoded by the MUC16 gene, is an ovarian cancer antigen widely used for a serum assay. Its extracellular region consists of tandem repeats of SEA domains. In this study we determined the three-dimensional structure of the SEA domain from the murine MUC16 homologue using multidimensional NMR spectroscopy. The domain forms a unique alpha/beta sandwich fold composed of two alpha helices and four antiparallel beta strands and has a characteristic turn named the TY-turn between alpha1 and alpha2. The internal mobility of the main chain is low throughout the domain. The residues that form the hydrophobic core and the TY-turn are fully conserved in all SEA domain sequences, indicating that the fold is common in the family. Interestingly, no other residues are conserved throughout the family. Thus, the sequence alignment of the SEA domain family was refined on the basis of the three-dimensional structure, which allowed us to classify the SEA domains into several subfamilies. The residues on the surface differ between these subfamilies, suggesting that each subfamily has a different function. In the MUC16 SEA domains, the conserved surface residues, Asn-10, Thr-12, Arg-63, Asp-75, Asp-112, Ser-115, and Phe-117, are clustered on the beta sheet surface, which may be functionally important. The putative epitope (residues 58-77) for anti-MUC16 antibodies is located around the beta2 and beta3 strands. On the other hand the tissue tumor marker MUC1 has a SEA domain belonging to another subfamily, and its GSVVV motif for proteolytic cleavage is located in the short loop connecting beta2 and beta3.
...
PMID:Solution structure of the SEA domain from the murine homologue of ovarian cancer antigen CA125 (MUC16). 1476 98

Inflammatory breast cancer (IBC) is a rare but very aggressive form of breast cancer. Its definition is based on clinical criteria, but a molecular definition could be useful when data are incomplete or features are missing. Recently, the identification of overexpression of E-cadherin in IBC has improved understanding of the molecular basis of this disease. Consequently, the aim of this study was to try to determine an immunophenotypic 'signature' of IBC. A series of 80 cases of IBC were compared with 552 non-IBC control cases and a model was elaborated to evaluate the probability of an inflammatory carcinoma being present in any clinical situation. Tissue microarrays (TMAs) were used to determine the immunohistochemical profile of eight proteins including E-cadherin, EGFR, oestrogen and progesterone receptor (ER and PR), MIB1, ERBB2, MUC1, and P53. All the parameters tested were differentially expressed between IBC and control cases in univariate analysis (p < 0.001). The five variables that were significantly associated with IBC in multivariate analysis were E-cadherin > or = 300 [HR = 5.64 (2.92-10.87)], ER negative [HR = 3.00 (1.67-5.51)], MIB1 > 20 [HR = 3.54 (1.87-6.71)], MUC1 cytoplasmic staining [HR = 2.72 (1.49-4.96)], and ERBB2 positive 2+ or 3+ [HR = 2.46 (1.26-4.78)]. The probability that a breast cancer with this full phenotype at diagnosis was an IBC was 90.5%. If any one of the five parameters was missing, this probability dropped to 75% and was less than 50% when one, two, or three parameters were present. The 5-year overall survival (OS) and 5-year disease-free survival (DFS) of patients with IBC were not significantly different from those of the non-IBC control group that expressed four or five parameters (nIBC-1), but this nIBC-1 control group had a significantly worse outcome than the non-IBC control group (nIBC-2) with only 0-3 parameters (p = 0.0049 for OS and p < 0.0001 for DFS). In conclusion, an immunophenotypic signature was suggested for IBC. This could help to determine the worst cases, independent of clinical criteria.
...
PMID:Immunophenotypic analysis of inflammatory breast cancers: identification of an 'inflammatory signature'. 1499 91

Inflammatory Breast Carcinoma (IBC) is a rare but aggressive form of breast carcinoma. Characteristic clinical and pathological features are well documented. Pathological response to chemotherapy is currently the only identified prognostic factor. This high-grade tumor exhibits phenotypical features of an aggressive tumor: absence of hormonal receptors in 56 to 83% of cases, high proliferating index, p53 expressed in 30 to 69%, Immunohistochemistry (IHC) detection of HER2 over expression in 38 to 60%. Current work on IBC points out specific molecular mechanisms: adhesion molecules such as E-Cadherin, apomucin MUC1 and angiogenesis processes contribute to the IBC phenotype. So does a gene named WISP3. This gene has been recently cloned and sequenced. It has been shown to be lost in IBC and could control tumor growth, invasion, and angiogenesis. This paper summarizes current knowledge on IBC and describes a new basis for a molecular definition of IBC.
...
PMID:[Inflammatory breast carcinoma: towards molecular characterization?]. 1509 94

We report 62 cases of invasive micropapillary carcinoma of the breast characterized by delicate pseudopapillary structures lacking a fibrovascular core and by tubuloalveolar structures freely floating in clear, empty spaces. All patients but 1 were women (median age, 57 years; range, 25-89 years). Tumor size ranged from 0.7 to 10 cm (median, 2.8 cm); 54 (87%) were grade 3. Psammoma bodies were identified in 29 (47%). Focal to massive lymphatic permeation was present in 39 (63%). Architectural features were retained in the node metastases, dermal lymphatics, and recurrences. Fifty-six patients (90%) had metastatic axillary nodes: 18 tumors were estrogen receptor-positive (32%); 11 were progesterone receptor-positive (20%); HER2/neu was overexpressed in 53 (95%) and p53 in 39 (70%). A peculiar immunoreactivity for MUC1 limited to the cytoplasmic membrane oriented toward the stroma and an absence of immunoreactivity for E-cadherin in the same side of the cytoplasmic membrane indicated inversion of cell polarization and a disturbance in the cell adhesion molecules. Of 41 patients with available follow-up, 29 (71%) had local recurrence (mean, 30 months) and 20 (49%) died of disease. These results underscore the aggressive behavior and poor prognosis of this breast carcinoma variant. Aggressive preoperative neoadjuvant chemotherapy should be considered.
...
PMID:Invasive micropapillary carcinoma of the breast: clinicopathologic study of 62 cases of a poorly recognized variant with highly aggressive behavior. 1519 58

The receptor tyrosine kinases (RTKs) RET, MET, and RON all carry the Met(p+1loop)-->Thr point mutation (i.e., 2B mutation), leading to the formation of tumors with high metastatic potential. Utilizing a novel antibody array, we identified constitutive phosphorylation of STAT3 in cells expressing the 2B mutation but not wild-type RET. MET or RON with the 2B mutation also constitutively phosphorylated STAT3. Members of the EPH, the only group of wild-type RTK that carry Thr(p+1loop) residue, are often expressed unexpectedly in different types of cancers. Ectopic expression of wild-type but not Thr(p+1loop)-->Met substituted EPH family members constitutively phosphorylated STAT3. In both RTK(Metp+1loop) with 2B mutation and wild-type EPH members the Thr(p+1loop) residue is required for constitutive kinase autophosphorylation and STAT3 recruitment. In multiple endocrine neoplasia 2B (MEN-2B) patients expressing RET(M918T), nuclear enrichment of STAT3 and elevated expression of CXCR4 was detected in metastatic thyroid C-cell carcinoma in the liver. In breast adenocarcinoma cell lines expressing multiple EPH members, STAT3 constitutively bound to the promoters of MUC1, MUC4, and MUC5B genes. Inhibiting STAT3 expression resulted in reduced expression of these metastasis-related genes and inhibited mobility. These findings provide insight into Thr(p+1loop) residue in RTK autophosphorylation and constitutive activation of STAT3 in metastatic cancer cells.
...
PMID:Central role of the threonine residue within the p+1 loop of receptor tyrosine kinase in STAT3 constitutive phosphorylation in metastatic cancer cells. 1548 8

Publicly available human genomic sequence data provide an unprecedented opportunity for researchers to decode the functionality of human genome. Such information is extremely valuable in cancer prevention diagnosis and treatment. Cancer Genome Anatomy Project (CGAP) and Gene Expression Omnibus (GEO) are two bioinformatic infrastructures for studying functional genomics. The goal of this study is to explore the feasibility of incorporating the Internet-available bioinformatic databases to discover human breast cancer-related genes. Several tools including the Gene Finder, Virtual Northern (vNorthern) and SAGE digital gene expression displayer (DGED) were used to analyze differential gene expression between benign and malignant breast tissues. A pilot study was performed using both EST and SAGE vNorthern to analyze the expression of a panel of known genes, including high abundance genes beta-actin and G3PDH, low abundance genes BRCA1 and p53, tissue-specific genes CEA and PSA and two breast cancer-related genes Her2/neu and MUC1. We found a high expression of beta-actin and G3PDH and a low expression of BRCA1 and p53 across different types of tissues as well as a tissue-specific expression of CEA in colon and PSA in prostate. A further analysis of 30 known breast cancer-related genes in breast cancer tissues by vNorthern demonstrated a high expression of oncogenes and low expression of tumor suppressor genes. An open-end analysis of two pools of breast cancer and benign breast tissue libraries by SAGE DGED produced 53 differentially expressed genes according to the screening criteria of a >five-fold difference and p<0.01. Further analysis by EST vNorthern and virtual microarray analysis reduced the candidate genes to six, with four down-regulated genes, ANXA1, CAV1, KRT5 and MMP7, and two up-regulated genes, ERBB2 and G1P3 in breast cancer. These findings were validated by a real-time RT-PCR analysis in eight paired human breast cancer tissue samples. We conclude that the combined multiple high throughput analyses is an effective data mining strategy in cancer gene identification. This approach may improve the usage of public available genomic data through strategic data mining of high throughput analysis.
...
PMID:In silico identification of breast cancer genes by combined multiple high throughput analyses. 1564 32


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

---