Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been reported previously that the bcl-2 protooncogene protein is detectable in neoplastic cells from cases of human lymphoma in which the 14;18 chromosomal translocation is present, but not in lymphomas that lack this chromosomal rearrangement or in normal lymphoid tissue. In the present study we confirmed, by immunohistologic labeling with polyclonal and monoclonal antibodies, that bcl-2 protein is strongly expressed in many cases of follicular lymphoma and that these neoplastic follicles differ clearly from their nonmalignant counterpart (reactive germinal centres) in which bcl-2 protein is undetectable. However we also found bcl-2 protein in normal T- and B-lymphoid cells and in a variety of lymphoproliferative disorders in which the 14;18 translocation is not present. It is therefore concluded that expression of bcl-2 protein is not a specific marker for lymphomas bearing the 14;18 chromosomal translocation and that the observations of other investigators may have reflected the inadequate sensitivity of their staining procedure.
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PMID:Expression of the bcl-2 oncogene protein is not specific for the 14;18 chromosomal translocation. 220 Nov 96

To determine the effect of oncogene expression on gamma radiation sensitivity of hematopoietic compared to fibroblastic cells, we selected clonal sublines of an interleukin-3 (IL-3)-dependent hematopoietic progenitor cell line 32D cl 3 and NIH/3T3 embryo fibroblastic cells following transfection with each oncogene linked to the mycophenolic acid resistance gene. Each mycophenolic acid-resistant subclone demonstrated high levels of specific poly(A)+ mRNA for each oncogene. The parent line 32D cl 3 demonstrated similar radiosensitivity at 116 cGy/min (D0 126, n 1.17) compared to 5 cGy/min (D0 123, n 1.65). This pattern was not altered in subclones of 32D cl 3 cells transfected with the epidermal growth factor (EGF) receptor gene and grown in EGF (at 116 cGy/min D0 104, n 0.998, at 5 cGy/min D0 115, n 1.09), or in 32D cl 3 cells expressing the v-sis oncogene (at 116 cGy/min D0 122.4, n 1.79, at 5 cGy/min D0 135, n 1.43). In contrast, expression of the transfected oncogenes v-erb-B, v-abl, or v-src conferred significant radioresistance at 5 cGy/min dose rate (D0 194, n 1.77; D0 165.5, n 1.56; D0 171, n 1.28, respectively). With the exception of v-sis, oncogene expression resulted in nonautocrine factor independence of 32D cl 3 subclones, and production of donor origin tumors in syngeneic new-born or adult mice. Two rare spontaneous factor-independent subclones of 32D cl 3 were also tested. Nonautocrine clone 32D cl 2 demonstrated significantly increased radioresistance at low dose rate (D0 186, n 1.63), while autocrine (IL-3 producing) subclone 32D cl 4 revealed no significant increase in radioresistance at 5 cGy/min. The parent fibroblast cell line NIH/3T3 showed an intrinsic relative radioresistance at low dose rate (at 5 cGy/min D0 157.3, n 1.81, compared to 116 cGy/min D0 134.3, n 1.57). Expression in NIH/3T3 of transfected oncogenes v-abl, v-fms, v-fos, or H-ras increased radioresistance at low dose rate (D0 208.6, n 1.61; D0 206.6, n 1.51; D0 167.5, n 1.85; and D0 206.8, n 1.08, respectively). Thus expression of each of several oncogenes induces resistance to gamma irradiation at 5 cGy/min in hematopoietic and fibroblast cell lines. These data may help explain the clinical recurrence of oncogene-expressing leukemia and lymphoma cells after marrow stem cell ablative doses of low-dose-rate total-body irradiation.
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PMID:Expression of transfected recombinant oncogenes increases radiation resistance of clonal hematopoietic and fibroblast cell lines selectively at clinical low dose rate. 232 Jul 25

Various kinds of lesions exist which should be discriminate from malignant or premalignant or borderline lesions. If there were a morphologic technical procedure on detection of malignant transformation of the cells at the initiation stage, before the lesion would develop a definitely identical with malignant lesion, such method must be most highly applicable for pathologists. DNA diagnosis has realized a warning of diagnosis of certain diseases or genetical maldevelopment prior to develop their clinical manifestation. Gene analysis has introduced in ++phragmatical screening test for certain diseases such as diabetes mellitus, thalassemia, T-cell leukemia or lymphoma, neuroblastoma, muscular dystrophy of Duchenne or Becker type, Ph' chromosome and so on. Immunohistochemical technology has provided an intracellular oncogene detection in some neoplastic malignancies such as n-myc in neuroblastoma. Amplification of c-erb B2 (also referred as neu and HER-2/neu) has indicated a higher malignant mammary carcinoma with poor-prognosis, even their size small and early stage. Oncogene analysis is expected to be available sperimposing on pathological morphology.
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PMID:[Detection of early stage cancer: pathological aspect with special reference to differential diagnosis]. 317 85

Proto-oncogenes represent a family of normal cellular genes that were identified on the basis of their similarity to genetic sequences with known tumorigenic or transforming potential. Accumulating evidence links alterations in either the structure, copy number, or expression of one or another of these genes to neoplasia. One such gene, called erbB-2/Her-2 was found amplified in an adenocarcinoma of the human salivary gland and has also been found associated with primary human breast cancer. Patients with multiple copies of the gene have had a shorter overall survival. In the present study, 21 tumors of the parotid gland were examined by Southern and Northern blot hybridization for amplification and possible overexpression of the erbB-2/Her-2 oncogene. Normal parotid gland tissue was used as negative control. The parotid gland lesions comprised 7 pleomorphic adenomas, 5 squamous cell carcinomas, 4 cases of chronic fibrotic sialadenosis, 3 mucoepidermoid carcinomas as well as 1 lymphoma and 1 cystadenolymphoma. Gene amplification was found in 1 of the pleomorphic adenomas, with 2 tumors showing a significant overexpression of the erbB-2/Her-2 oncogene. Because 3-5% of all pleomorphic adenomas undergo malignant transformation, close follow-up of patients is currently underway.
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PMID:erbB-2/Her-2 gene amplification and overexpression in parotid gland tumors. 810 55

Multiple myeloma (MM) is the most common plasma cell dyscrasia. Conventional therapy results in a median survival of 3-5 years. Patients with B-cell disorders and coexistent HER-2/neu overexpression in solid tumors have a poorer prognosis than those without an underlying B-cell disorder. This, and the recent success of the tyrosine kinase inhibitor, imatinib mesylate in chronic myelogenous leukemia, led us to evaluate the incidence and role of c-kit (CD117) and HER-2/neu overexpression in MM. We conducted a retrospective study to determine the incidence of HER-2/neu and c-kit overexpression in MM. HER-2/neu overexpression was evaluated using the DAKO Hercep test and c-kit overexpression was assessed using conventional immunohistochemistry (IHC); 69 patients with a diagnosis of MM were identified, of whom, 31 patients (19 males and 12 females) had an adequate pathological specimen available for IHC testing; 4 out of 31 patients (12.9%) showed HER-2/neu overexpression, while 5/31 (16.13%) showed CD117 expression. Two patients (6.45%) showed both HER-2/neu and c-kit overexpression. Although both HER-2/neu and c-kit are not expressed very frequently in patients with MM, there appears to be a subgroup of patients in whom, either one or both these oncogenes is overexpressed. Given our small sample size, it is difficult to comment on the effect of CD117 and/or HER-2/neu overexpression on survival. Future larger studies are needed to define the association in MM and to determine if the presence of one (CD117 or HER-2/neu) has an effect on overexpression of the other oncoprotein. Furthermore, it would be beneficial to identify the molecular nature of the interplay between HER-2/neu and c-kit, if any. Target-directed signal transduction inhibition therapy using tyrosine kinase inhibitors, may be a distinct possibility in a select group of patients with MM.
Leuk Lymphoma 2002 Dec
PMID:Immunohistochemical identification of HER-2/neu overexpression and CD117 (c-kit) expression in multiple myeloma. 1261 38

This report describes the profiling of proteins in a sample prepared by laser capture microdissection (LCM) from a breast cancer cell line (SKBR-3). This experimental approach serves as a model system for proteomic studies on selected tissue samples and for studies of specific cell types. The captured cells were isolated in a dehydrated and reduced state and solubilized with a denaturing buffer. After dilution the protein mixture was digested with trypsin and the resulting peptide mixture was fractionated by reversed phase HPLC (RPLC) and analyzed on an ion trap mass spectrometer. A key part of this study is the combination of the LCM process with an extraction/digestion procedure that allowed effective solubilization of a significant part of the cellular sample in a single step. The identity of the peptides was determined by tandem mass spectrometry measurements in which the resulting spectra were compared with genomic and proteomic databases and protein identifications were made. While only peptides with a high probability assignment were used, the interpretation of mass spectral fragmentation patterns were also confirmed by manual interpretation of the spectra. Also, for the more abundant proteins the initial protein assignment from the best match peptide was strengthened by the observation of additional confirmatory peptide identifications. Another selection criteria was correlation of the mass spectrometric studies with clinical and genomic studies of potential cancer markers in tumor samples. This proteomic study allowed identification of the following proteins: human receptor protein kinase HER-2 or ERBB-2 and related kinases HER-3 and HER-4, the gene products from breast cancer type I and II susceptibility genes and cytoskeletal components such as cytokeratins 8, 18 and 19. Other proteins include fibroblast growth factor receptor variants (FGFR-2&4) and T-lymphoma invasion and metastasis inducing protein 1 (TIAM1). In addition several nonreceptor protein kinases YES, FAK and JAK-1 and 3 were identified. Since the study was performed on a limited number of cells (approximately 10,000) it raises the possibility of such studies being performed on individual patient samples prepared by needle biopsy.
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PMID:An approach to the proteomic analysis of a breast cancer cell line (SKBR-3). 1283 28

Immunostimulatory CpG oligodeoxynucleotides (ODNs) can enhance the therapeutic effect of monoclonal antibodies (mAbs) by enhancing antibody-dependent cell-mediated cytotoxicity (ADCC). Distinct classes of CpG ODNs have been found recently to stimulate different effector cell populations. We used murine cancer models to explore the role of various effector cell populations in the antitumor activity seen with mAbs combined with CpG ODNs of the A and B classes. In the 38C13 syngeneic murine lymphoma model, both CpG A and CpG B enhanced the efficacy of murine antilymphoma mAb. Depletion of natural killer (NK) cells alone markedly decreased the efficacy of therapy with mAbs plus CpG A. In contrast, depletion of both NK cells and granulocytes was required to decrease the efficacy of mAb plus CpG B. A human (h) Fc gamma receptor I (FcgammaRI)-expressing transgenic (Tg) mouse model was used to explore the role of FcgammaRI in therapy with mAb and CpG ODN. CpG B induced up-regulation of FcgammaRI in hFcgammaRI Tg mice, whereas CpG A did not. In vitro CpG B also enhanced ADCC of HER-2/neu-expressing tumor cells by the FcgammaRI-directed bispecific antibody MDX-H210 using hFcgammaRI-positive effector cells. In a solid tumor model, tumor growth was inhibited in Tg mice treated with a combination of MDX-H210 and CpG B. These data suggest that CpG A enhance ADCC largely by activating NK cells. In contrast, other effector cell populations, including granulocytes, contribute to the antitumor activity of CpG B and mAbs. FcgammaRI plays an important role in this activity.
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PMID:CpG-A and B oligodeoxynucleotides enhance the efficacy of antibody therapy by activating different effector cell populations. 1450 Apr

Cisplatin and its analogues are the most commonly used agents in the treatment of head and neck squamous cell carcinoma. In this study, we investigated a possible role of epidermal growth factor (EGF) receptor (EGFR) phosphorylation and degradation in cisplatin-induced cytotoxicity. Cisplatin treatment led to an increase in initial EGFR phosphorylation at Y1045, the binding site of ubiquitin ligase, Casitas B-lineage lymphoma (c-Cbl), followed by ubiquitination in the relatively cisplatin-sensitive cell lines. However, cisplatin-resistant cell lines underwent minimal EGFR phosphorylation at the Y1045 site and minimal ubiquitination. We found that EGFR degradation in response to cisplatin was highly correlated with cytotoxicity in seven head and neck cancer cell lines. Pretreatment with EGF enhanced cisplatin-induced EGFR degradation and cytotoxicity, whereas erlotinib pretreatment blocked EGFR phosphorylation, degradation, and cisplatin-induced cytotoxicity. Expression of a mutant Y1045F EGFR, which is relatively resistant to c-Cbl-mediated degradation, in Chinese hamster ovary cells and the UMSCC11B human head and neck cancer cell line protected EGFR from cisplatin-induced degradation and enhanced cell survival compared with wild-type (WT) EGFR. Transfection of WT c-Cbl enhanced EGFR degradation and cisplatin-induced cytotoxicity compared with control vector. These results show that cisplatin-induced EGFR phosphorylation and subsequent ubiquitination and degradation is an important determinant of cisplatin sensitivity. Our findings suggest that treatment with an EGFR inhibitor before cisplatin would be antagonistic, as EGFR inhibition would protect EGFR from cisplatin-mediated phosphorylation and subsequent ubiquitination and degradation, which may explain the negative results of several recent clinical trials. Furthermore, they suggest that EGFR degradation is worth exploring as an early biomarker of response and as a target to improve outcome.
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PMID:Role of epidermal growth factor receptor degradation in cisplatin-induced cytotoxicity in head and neck cancer. 2021 22

The human epidermal growth factor (EGF) receptor (HER) family consists of four receptors that bind to ligands sharing an EGF-like motif. The HER family of receptor tyrosine kinases and their ligands (EGF family) are known to play a significant role in gastrointestinal cancer. In particular, the EGF receptor, HER1, is one of the main candidates for the molecular-targeted therapy of colon cancer, and HER2 is a candidate for the treatment of gastric cancer which overexpresses HER2. In contrast, the role of the HER and EGF families in malignant lymphoma has not been fully elucidated. In this study, we investigated the expression and function of the HER and EGF families in lymphoma cell lines and tumor samples. Reverse transcription polymerase chain reaction revealed that the ligands for HER1 were mainly expressed in gastric cancer and colon cancer cell lines, but not in lymphoma cell lines. On the other hand, the EGF family member, neuregulin (NRG) 4, was highly expressed in lymphoma cell lines. Immunohistochemical analyses of malignant lymphoma clinical samples revealed that NRG4 and HER4 were mainly expressed in mucosa-associated lymphoid tissue (MALT) and follicular lymphoma. Immunoprecipitation of Raji and Daudi cell lines revealed that recombinant NRG4 induced the tyrosine phosphorylation of HER4. Additionally, recombinant NRG4 activated the proliferation of lymphoma cell lines. These findings suggest that the NRG4-HER4 axis plays a major role in the proliferation of malignant lymphoma cells in the gastrointestinal tract.
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PMID:The role of neuregulin4 and HER4 in gastrointestinal malignant lymphoma. 2180 36

We describe here a case of malignant lymphoma (ML) which coexpressed common acute lymphoblastic leukemia antigen (CALLA:CD10) and NRAS p21 and c-erbB-2 (neu) oncogene products. The patient, an 83 year-old man, had massive generalized lymphadenopathy and pleural effusions. Serum LDH levels were elevated to 801 IU/L. Surface phenotypes were analysed by a fluorescent-activated cell sorter with a panel of monoclonal antibodies (MAbs). The ML cells coexpressed antigens detected by MAbs CD10, CD19, CD20, CD22, CD24, CD38, Ia (HLA-DR), c-neu and surface immunoglobulin (Ig) G, Kappa. Gene rearrangements for the Ig JH and JK were found. Overexpression of NRAS p21 was shown by gene amplification using Southern blot analysis, while gene amplification of c-erbB-2 oncogene was also demonstrated. To our knowledge, this is the first report to demonstrate an overexpression of p185 c-neu on ML cells. These findings suggest that the p185 neu may be a prognostic indicator not only for breast adenocarcinomas but also for lymphoproliferative disorders, and that the transforming p185 protein may be involved in the mechanisms of aggressive expansion of lymphoid neoplasias.
Leuk Lymphoma 1991
PMID:Aggressive Diffuse Lymphoma Coexpressing NRAS p21 and C-erbB-2 (neu) Oncogene Products, and CALL A (CD 10). 2746 77


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