Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The number and distribution of Leu-7 + cells, a subset of Natural Killer cells clustered as CD 57 + cells, were studied with an immunoperoxidase technique on reactive lymph nodes (n = 13), malignant lymphomas (n = 60) and Hodgkin's disease (n = 22). Results of paraffin-section immunocytochemistry were compared with those obtained of frozen sections of the same tissues. CD 57 + cells are small lymphocytes mainly located in the germinal centers of reactive lymph nodes and in their malignant counterpart, i.e. the follicular lymphomas. The paragranuloma of Hodgkin's disease, type I nodular, contained high numbers of CD 57+ cells. Nine cases of CD 57+ lymphomas are reported, which were of high grade of malignancy. Their histological subtypes were anaplastic (3 cases) immunoblastic (2 cases), pleomorphic medium and large cell (3 cases), unclassifiable (1 case). Their diverse T-cell (4 cases) or B-cell (2 cases) origin and the various expression of epithelial membrane antigen (EMA) or Kil/Ber-H2 (CD 30) suggest an aberrant CD 57+ phenotype of a subset of large cell lymphomas.
 ...
PMID:[Cells of the phenotype HNK-1 + (CD 57 +) in reactive adenopathies, lymphomas and Hodgkin's disease]. 169 23

In order to study the antigenicity of envelope 46 kDa glycoprotein (gp46) of human T-cell leukemia virus type-I (HTLV-1), we have generated monoclonal anti-gp46 antibodies (MAbs), REY-7, REY-11, REY-16, REY-30, MET-2 and MET-3 from rats and mice. Immunoblot and immunofluorescence assays showed that these MAbs recognize gp46 and its related antigens, and specifically stained HTLV-I-bearing cells. All MAbs reacted with a recombinant gp46 antigen, N147, expressing the 147 amino acids in the C-terminal half of gp46. By using various synthetic peptides corresponding to the gp46 sequence, epitopes recognized by REY-7 and MET-3, REY-11 and REY-16, and REY-30 were mapped to regions corresponding to the amino acids 175-199, 253-282 and 288-312, respectively. MET-2 did not react with any of the peptides used. These results indicate that the present MABs are directed against at least 4 distinct epitopes expressed on the C-terminal half of gp46. The binding of these MAbs to gp46 was specifically inhibited by sera from HTLV-I-infected individuals, but none of these MAbs inhibited the cell fusion activity of HTLV-I.
Int J Cancer 1990 Oct 15
PMID:Generation and characterization of monoclonal antibodies against multiple epitopes on the C-terminal half of envelope gp46 of human T-cell leukemia virus type-I (HTLV-I). 169 31

HER2 or c-erbB-2 is a putative growth factor receptor with sequence homology to the epidermal growth factor receptor. It is the human homologue of the rat protooncogene neu and may have an important role in human malignancies such as breast and ovarian cancers. Like other growth factor receptors, HER2 has intrinsic protein tyrosine kinase activity and undergoes autophosphorylation. Recently, we have demonstrated that, similar to the epidermal growth factor receptor, all autophosphorylation sites of HER2 are localized in the carboxyl terminus of this protein. In the present study, immunopurified HER2 was allowed to autophosphorylate, and tryptic phosphopeptides were generated. After purification of these phosphopeptides by high performance liquid chromatography, microsequencing was performed. Utilizing this approach, two autophosphorylation sites were unequivocally identified at Y1023 and Y1248. The sequences of two other tyrosine phosphorylated tryptic peptides were determined, but the exact site of autophosphorylation could not be determined because multiple tyrosines were located on each peptide. However, each of these peptides contains tyrosines that correspond to major autophosphorylation sites of the epidermal growth factor receptor, suggesting that, in addition to Y1023 and Y1248, Y1139 and Y1222 also serve as autophosphorylation sites of HER2.
 ...
PMID:Identification of autophosphorylation sites of HER2/neu. 170 16

We examined 35 primary human ovarian adenocarcinomas for the presence of epidermal growth factor (EGF) receptor (EGFR) in plasma membranes from cancer tissues by using 125I-EGF as a ligand. Specific 125I-EGF bindings were observed in 20 (57%) of these 35 cases. Scatchard analysis showed a class of high affinity EGF receptor: Kd 5.0 +/- 1.0 x 10(-10) M; Bmax, 83.3 +/- 12.1 fmol/mg protein (mean +/- SE, n = 20). Northern analysis in polyadenylated RNA from 15 EGFR(+) cancers using pretransforming growth factor alpha (pre-TGF alpha), prepro-EGF complementary DNA, and pE7, a complementary DNA clone of human EGFR, as probes revealed that pre-TGF alpha and EGFR mRNAs but not prepro-EGF mRNA were expressed in all cases examined. Immunocytochemical studies using monoclonal antibodies (mAbs) against TGF alpha, EGF, and EGFR showed that TGF alpha and EGFR but not EGF proteins were present on ovarian cancer cells in all cases. These data suggested a possible TGF alpha/EGFR autocrine mechanism in EGFR(+) ovarian cancers. We, therefore, examined the biological significance of this autocrine mechanism by using primary monolayer cell cultures. In primary cultures from EGFR (+) cancers, TGF alpha added to the culture medium stimulated the [3H]thymidine incorporation dose dependently. Moreover, the addition of mAbs against TGF alpha and EGFR but not EGF inhibited [3H]thymidine incorporation dose dependently in EGFR(+) cancer cells. On the other hand, in primary cultures from EGFR(-) cancers, TGF alpha and anti-TGF alpha, -EGFR, and -EGF mAbs did not show any effects on [3H]thymidine incorporation. All these results suggested the possible crucial role of a TGF alpha/EGFR autocrine growth mechanism in primary human ovarian cancers which express EGFR.
Cancer Res 1991 Oct 01
PMID:Evidence for the involvement of transforming growth factor alpha and epidermal growth factor receptor autocrine growth mechanism in primary human ovarian cancers in vitro. 171 46

The ERBB2 (also called HER2, neu, and c-erbB-2) gene product, which encodes a growth factor receptor, was implicated in the malignancy of human adenocarcinomas. An antibody directed to the rat oncogenic receptor has been previously shown to have an antitumor effect in model systems. In an attempt to extend this observation to the protooncogenic human receptor and also to understand the underlying mechanism, we generated a panel of monoclonal antibodies specific to the extracellular portion of the ERBB2 protein. The effects of the antibodies on tumor growth were compared with their cellular and biochemical actions in vitro. Surprisingly, opposing in vivo effects were observed: although some antibodies almost completely inhibited the growth in athymic mice of transfected murine fibroblasts that overexpress Erbb-2, other antibodies either accelerated tumor growth or resulted in intermediate responses. When tested on cultured human breast carcinoma cells or ERBB2 transfectants, the tumor-stimulatory antibody was found to induce significant elevation of tyrosine phosphorylation of the ERBB2 protein. In contrast, only partial correlation was observed between the capacity to restrict tumor growth and the effects of the antibodies on receptor degradation and cellular proliferation in vitro. This suggests that the antitumor antibodies affect both receptor function and host-tumor interactions. Our results may help establish experimental criteria for the selection of specific antibodies for use either alone or in conjunction with other molecules as pharmacological antitumor agents.
 ...
PMID:Mechanistic aspects of the opposing effects of monoclonal antibodies to the ERBB2 receptor on tumor growth. 171 84

Although transforming growth factor (TGF) alpha and epidermal growth factor (EGF) receptor (EGFR) autocrine mechanism is widely demonstrated in many kinds of cancers, its biological significances still remain circumstantial. We critically assessed the significance of this mechanism on the growth of an ovarian cancer cell line. Northern blot analysis in polyadenylated RNA isolated from cells by using 32P-labeled pre-TGF alpha, EGRF, and prepro-EGF complementary DNAs as probes revealed that pre-TGF alpha and EGFR but not prepro-EGF gene transcripts were expressed in the cell. TGF alpha and EGFR but not EGF proteins were observed by immunocytochemical stainings, using monoclonal antibodies against human TGF alpha, EGFR, and EGF, respectively. This cell line possessed a class of high affinity EGF receptor by 125I-EGF binding studies; Kd being 2.9 x 10(-10) M and Bmax to be 7.7 x 10(4) sites/cell. As much as 1.12 +/- 0.14 ng (SD; n = 3)/10(7) cells/24 h of TGF alpha was secreted in the conditioned media. These results suggested the expression of a TGF alpha/EGFR autocrine mechanism in this cell line. We, therefore, assessed the biological significance of this mechanism on the growth of this cell line in serum-free monolayer cell cultures. Although 0.1, 1.0, and 10 nM concentrations of TGF alpha did not show significant growth promotion, monoclonal antibodies against TGF alpha and EGFR but not EGF significantly inhibited cell growth. All these data suggested the biological importance of a TGF alpha/EGFR autocrine mechanism on the growth of this cell line in vitro.
Cancer Res 1991 Nov 01
PMID:Involvement of transforming growth factor alpha/epidermal growth factor receptor autocrine growth mechanism in an ovarian cancer cell line in vitro. 171 91

The expression of protein-tyrosine kinases (PTKs; ATP:protein-tyrosine O-phosphotransferase, EC 2.7.1.112) was studied in normal human lung and various tumors by PCR followed by molecular cloning and sequence analysis. Six known PTKs (YES, FGR, LYN, HCK, PDGFB-R, and CSF1-R), as well as two additional members of this enzyme family, were detected in lung. One of the newly discovered sequences appears to represent a group of cytosolic PTKs. The cDNA sequence of the second unknown PTK revealed that it is a fourth member of the fibroblast growth factor receptor family. It was therefore called TKF (tyrosine kinase related to fibroblast growth factor receptor). Among a wide variety of cells and tissues tested, including human lymphocytes and macrophages, TKF was only found expressed in lung. Apart from normal lung, TKF expression could be demonstrated in some tumors of lung origin, but also in malignancies not derived from lung tissues. As fibroblast growth factors are generally involved in a variety of functions such as mitogenesis, angiogenesis, and wound healing, the specific expression of a receptor-related gene in lung only may point to yet another special function of this group of proteins.
 ...
PMID:Two additional protein-tyrosine kinases expressed in human lung: fourth member of the fibroblast growth factor receptor family and an intracellular protein-tyrosine kinase. 172 May 39

Growth factor(s) with a strong mitogenic effect on BALB/c3T3 cells was purified from an extract of C-Li21 cells, a human hepatocellular carcinoma line, by a combination of heparin-affinity chromatography and reversed-phase high-performance liquid chromatography (HPLC). Two major peaks of mitogenic activity were obtained by reversed-phase HPLC. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of the two peaks revealed that one was composed of three proteins with relative molecular masses of 27, 24 and 23 kilodaltons (kD), whereas the other was a single 19-kD protein. Immunoblot analysis showed that all four of these molecules were immunoreactive species of human basic fibroblast growth factor (bFGF). N-Terminal sequence analysis of these molecules revealed that most of them were N-terminally blocked. However, small proportions of the 23- and 19-kD molecules were not blocked, and their respective N-terminal sequences were found to correspond to Gly-40-Gly-27 and Pro29-Phe40 of human bFGF deduced from the cDNA sequence of a human hepatoma cell line, SK-HEP-1. Expression of bFGF in hepatocellular carcinomas was then investigated by RNA blot analysis. All of the examined hepatocellular carcinoma cells expressed bFGF, and the degree of expression was higher in surgically resected hepatocellular carcinomas than in the corresponding adjacent non-cancerous liver tissue. Transcripts of bFGF were not detected in normal liver. These results suggest that C-Li21 cells produce four molecular forms of bFGF, and that bFGF may be involved in hepatocarcinogenesis. Moreover, it appears that bFGF is a potent mitogen toward primary-cultured hepatocytes, and that high-molecular-mass forms of bFGF produced by C-Li21 cells have stronger mitogenic effects on hepatocytes and are more stable under acidic conditions than the low-molecular-mass form, composed of 146 amino acids.
Jpn J Cancer Res 1991 Nov
PMID:Characterization of high-molecular-mass forms of basic fibroblast growth factor produced by hepatocellular carcinoma cells: possible involvement of basic fibroblast growth factor in hepatocarcinogenesis. 172 15

We report a linkage between cell aggressiveness, protein kinase C (PKC) activity, tyrosine kinase (PTK) activity and serum requirement. We used 2 leukemic cell lines induced by Moloney murine leukemia virus (MLV). One line was highly aggressive (BS-24-1) and required low serum concentrations (3%) for optimal growth in comparison to the less aggressive line (RO2T) that needed 10% serum for optimal growth. The more malignant cells exhibited higher PKC and PTK activity. This activity was independent of serum concentration between 0.01-10%. In contrast, the weakly malignant cells need a high serum concentration (10%) for optimal PKC or PTK activity. Immunoblot analysis revealed a higher level of PKC protein in the BS-24-1 cells than in the RO2T cells. Serum induction of PKC activity did not change the amount of PKC protein in the cytosol or the membrane fractions, indicating post-translational mechanism regulation of PKC. We suggest that the aggressiveness of BS-24-1 resulted from its ability to become independent of growth regulation by serum factors, via autocrine stimulation of PKC and PTK.
Int J Cancer 1992 Jan 02
PMID:Elevated activities of protein kinase C and tyrosine kinase correlate to leukemic cell aggressiveness. 172 4

Amplification of the c-myc and HER2/neu genes was found in 20 and 23%, respectively, of primary breast cancer tissues derived from 282 patients (median follow-up, 74 months). c-myc amplification was observed more frequently in larger tumors (P = 0.01) and in lymph node-positive patients (P = 0.01) but was not associated with age, menopausal status, or with differentiation grade or steroid receptor status. c-myc amplification was strongly negatively correlated with HER2/neu amplification (P less than 0.001). In univariate analysis, amplification of c-myc proved to be a significant predictor of reduced relapse-free and overall survival (for both, P less than 0.001). In multivariate analysis for relapse-free survival, c-myc amplification significantly (P = 0.001) added to the prognostic power of tumor size (P less than 0.001), lymph node status (P less than 0.001), and estrogen receptor status (P = 0.003), with the highest relative failure rate (1.8) after lymph node status (2.2). In this pilot study, c-myc amplification was predictive for outcome, especially among patients with node-negative disease or steroid receptor-positive tumors; 51 and 46% differences in actuarial 5-year recurrence rates when compared to patients with tumors with normal c-myc gene copy numbers, respectively. HER2/neu amplification was not associated with relapse-free survival but weakly with shorter overall survival in univariate analysis (P = 0.035). Only in the relatively small subgroup of steroid receptor-negative tumors, HER2/neu amplification may identify those patients with an increased risk of death. In conclusion, amplification of c-myc is an independent powerful prognosticator, particularly in node-negative and steroid receptor-positive breast cancer, whereas HER2/neu amplification may be of limited prognostic value, only in steroid receptor-negative disease.
Cancer Res 1992 Mar 01
PMID:c-myc amplification is a better prognostic factor than HER2/neu amplification in primary breast cancer. 173 70


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