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)

We have reported previously that human group C adenoviruses down-regulate the epidermal growth factor (EGF) receptor (EGF-R) (C. R. Carlin, A. E. Tollefson, H. A. Brady, B. L. Hoffman, and W. S. M. Wold, Cell 57:135-144, 1989). Expression of a 13.7-kDa protein encoded by a gene in the E3 transcription unit is necessary and sufficient for this effect (Carlin et al., Cell, 1989; B. L. Hoffman, A. Ullrich, W. S. M. Wold, and C. R. Carlin, Mol. Cell. Biol. 10:5521-5524, 1990). We show here that EGF-R down-regulation is accelerated in cells which overexpress the receptor when these cells are infected with virus mutants that overproduce the 13.7-kDa protein compared with wild-type virus. This is in contrast to EGF stimulation, for which others have shown that high concentrations of ligand are associated with low rates of receptor internalization in EGF-R-overexpressing cells (D. Kuppuswamy and L. J. Pike, J. Biol. Chem. 264:3357-3363, 1989; H. S. Wiley, J. Cell Biol. 107:801-810, 1988). We also show that the E3 protein is not present in media conditioned by infected cells and that it does not induce secretion of an EGF-like autocrine factor. Moreover, while mature membrane-bound EGF-R is down-regulated, the precursor of the membrane-bound form is not. Adenovirus infection also does not affect receptor-related molecules expressed in the secretory pathway. Interestingly, adenovirus-induced down-regulation is not regulated by concentrations of EGF associated with a slow rate of internalization in A431 cells. This suggests that 13.7-kDa protein expression triggers receptor entry by a novel ligand-independent pathway or, alternatively, that it compensates for a cellular factor that may be rate limiting during EGF-mediated endocytosis.
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PMID:Evidence for intracellular down-regulation of the epidermal growth factor (EGF) receptor during adenovirus infection by an EGF-independent mechanism. 172 83

The combination of specific gene targeting technologies with efficient gene delivery systems could provide the means to evaluate the concept of anticancer strategies designed to block expression of potentially rate-limiting tumor promoting factors. Here, we constructed adenoviruses expressing hammerhead-ribozymes targeted to two of these factors, the tyrosine kinase receptor HER-2/neu or the growth factor pleiotrophin (PTN). Adenovirus-mediated transduction of either HER-2/neu- or PTN-targeted ribozymes depleted the respective RNAs and inhibited protein expression significantly in three different human cancer cell lines. This resulted in almost complete abrogation of HER-2/neu- or PTN-dependent cancer-cell proliferation, thus demonstrating the feasibility of this approach as a future cancer gene therapy.
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PMID:Adenovirus-mediated transduction of ribozymes abrogates HER-2/neu and pleiotrophin expression and inhibits tumor cell proliferation. 934 31

The aim of this study was to investigate therapeutic efficacy of adenovirus-mediated E1a gene therapy for ovarian cancer in vitro and in vivo. Recombinant replication-deficient adenoviral vectors were prepared by superinfection of 293 cells, and then purified. The efficacy of the adenovirus vector system to infect ovarian cells was tested using different multiplicity of infection (MOI) and different times (1-4) of Ad.RSVlacZ. SKOV-3 cells (10(3) per well) were infected once with 2 x 10(4) adenovirus. The cells were harvested and counted on different days for 7 days to generate the in vitro growth curve. Tumor-bearing mice were injected intraperitoneally with ovarian cancer cells and treated by intraperitoneal injection of 100 microl (2.5 x 10(8) PFU) viral solution containing either replication-deficient Ad.E1a(+); control virus Ad.E1a(-) which is the same adenovirus as Ad.E1a(+) except for E1a deletion, or just phosphate buffered solution. The transduction efficacy increased with higher MOI and reached a plateau at the 20:1 ratio. When Ad.E1a(+) was used to transduce the HER-2/neu overexpressing human ovarian cancer cell line SKOV-3, tumor cell growth in vitro was greatly inhibited by E1a transduction. Also, Ad.E1a+ greatly inhibited tumor growth of SKOV-3-bearing mice. Immunohistochemistry analysis indicated that Ad.E1a protein was expressed in tumor tissue and expression of HER-2/neu p185 protein was suppressed. Very strong beta-gal staining was detected in tumors, and beta-gal activity in small intestine, lung, heart, stomach, liver, and kidney was detected. No beta-gal activity was detected in the tumor and other organs in control mice injected with Ad.E1a(-) or PBS. Adenovirus-type 5 E1a gene can efficaciously inhibit HER-2/neu-overexpressing ovarian cancer, and this promising procedure could greatly benefit ovarian cancer patients with high expression of HER-2/neu.
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PMID:Adenovirus 5 E1a-mediated gene therapy for human ovarian cancer cells in vitro and in vivo. 1128 29

Pet dogs represent a valuable pre-clinical model to assess the efficacy of oncology drugs. Additionally, canine cancers occur with an incidence similar to that of humans and share many features with human malignancies including histological appearance, tumor genetics, biological behavior and response to conventional therapies. The telomerase reverse transcriptase (TERT) is reactivated in most of human and dog tumors. Similarly, HER-2/neu oncoprotein is overexpressed in a proportion of canine breast cancers. Therefore, TERT and HER-2/neu can constitute valid tumor associated antigens (TAA), suitable targets for translational cancer immunotherapy in dogs. In this study, we have evaluated the ability of DNA electroporation (DNA-EP) and Adenovirus serotype 6 (Ad6) to induce immune responses against dog TERT (dTERT) and HER-2/neu in healthy dogs. Vaccination was effective in all treated animals and the adaptive immune response remained detectable and long-lasting in the absence of autoimmunity or other side-effects. Our results show that DNA-EP/Ad6-based cancer vaccine induces adaptive immune responses against TAA in canine subjects and support further evaluation of this approach in cancer dog patients.
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PMID:Telomerase and HER-2/neu as targets of genetic cancer vaccines in dogs. 1994 91