Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:O76050 (neu)
 3,969 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In nontransformed DHFR/G-8 cells (NIH 3T3 cells transfected with normal rat neu gene), the normal neu gene product was initially synthesized as a 170-kDa protein bearing endoglycosidase H-sensitive oligosaccharide chains and was then processed to a 175-kDa mature form with endoglycosidase H-resistant, endoglycosidase F-sensitive oligosaccharide chains. Most of this 175-kDa mature form appeared on the cell surface 2 h following synthesis and showed a half-life of approximately 3 h. In the presence of a growth factor(s) partially purified from bovine kidney, the half-life of this 175-kDa normal neu gene product was shortened to less than 30 min. In B104-1-1 cells (NIH 3T3 cells transfected with neu gene activated oncogenically by a point mutation that changes a valine residue to a glutamic acid residue in the putative transmembrane region), the oncogenically activated neu gene product was also synthesized as a 170-kDa precursor with endoglycosidase H-sensitive oligosaccharide chains. However, this 170-kDa precursor diminished very fast and was only partially processed to a 185-kDa mature form which exhibited a half-life of less than 30 min. The 185-kDa activated neu gene product possessed an unidentified post-translational modification in addition to N-linked oligosaccharide chains. Both the precursor and mature forms of the mutationally activated neu gene product showed increased tyrosine-specific phosphorylation as compared with those of their normal counterparts in DHFR/G-8 cells. The mutationally activated neu gene product in B104-1-1 cells shared several features which have been reported previously for the ligand-activated platelet-derived growth factor receptor in v-sis- or c-sis-transformed cells. These properties include: 1) accelerated turnover of the precursor and mature forms compared with the rates of turnover of its normal counterparts, 2) insensitivity of this rapid turnover to lysosomotropic amines, and 3) increased in vivo tyrosine-specific phosphorylation of both the precursor and mature forms. These findings suggest that the mutationally activated neu gene product may transform the cells by mimicking ligand-induced activation.
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PMID:Differential processing and turnover of the oncogenically activated neu/erb B2 gene product and its normal cellular counterpart. 196 62

Previously reported studies have suggested that variations in the pattern of proto-oncogene expression within a specific tumor type may denote an underlying difference in the biology and clinical behavior of those tumors. To more sensitively characterize malignant tumors of the central nervous system, we have used Northern blot hybridization analysis to determine the patterns of expression of seven proto-oncogenes in 20 cell lines established from biopsy specimens of patients with malignant glioma. The following proto-oncogenes are expressed at detectable levels in 30 micrograms of total RNA from most glioma cell lines examined: c-myc (20/20), c-mil/raf-1 (18/18), neu (19/20), c-erbB (19/20), and c-myb (17/20). In contrast, only half of the cell lines expressed detectable c-sis (10/20). In none of the cell lines tested was N-myc (0/20) mRNA detected. Morphologic analysis of these 20 cell lines revealed three different growth patterns: bipolar, epithelial, and pleomorphic-glial. Detectable levels of c-sis mRNA typically occurred with either an epithelial or pleomorphic-glial morphology. The pleomorphic-glial subgroup was also characterized by the expression of glial fibrillary acidic protein.
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PMID:Patterns of proto-oncogene expression in human glioma cell lines. 281 Mar 98

Dsi-1 is a region of chromosomal DNA that underwent proviral insertion in 3 of 24 Moloney murine leukemia virus-induced rat thymomas. In one of these tumors, a provirus is also integrated adjacent to the proto-oncogene c-myc. The proviruses in Dsi-1 have been characterized and appear to be complete. The proviruses were located within a 2-kilobase region that contained four prominent DNase I-hypersensitive sites. These hypersensitive sites were observed in Moloney murine leukemia virus-induced thymomas but not in NRK cells. The region of Dsi-1 immediately 3' to the insertions cross-hybridized with human and chicken DNA, indicating that it contains highly conserved sequences. No evidence could be found for the expression of this highly conserved region. Dsi-1 was mapped to mouse chromosome 4. This location demonstrates that Dsi-1 is different from 16 of the known proto-oncogenes (c-abl, c-erbA c-erbB, c-ets-1, c-ets-2, c-fes, c-fos, c-myb, c-myc, c-raf, A-raf, c-Ha-ras, c-Ki-ras, N-ras, c-sis, and c-src) and 12 cellular regions of tumor-associated integrations in retrovirus-induced tumors (c-erbB, Fis-1, int-1, int-2, Mis-1/pvt-1, Mlvi-1, Mlvi-2, c-mos, c-myb, c-myc, Pim-1, and c-Ha-ras). Hybridization experiments indicated that Dsi-1 is probably different from five additional proto-oncogenes (c-fgr, c-fms, c-mos, neu, and c-yes) and from two additional frequent integration regions (lck and Mlvi-3).
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PMID:Dsi-1, a region with frequent proviral insertions in Moloney murine leukemia virus-induced rat thymomas. 302 11

To determine if the tumor suppressor gene active in BHK hamster cells acts to maintain the normal phenotype by influencing oncogene transformation, careful, quantitative transfections with a variety of oncogenes were performed on four closely related BHK subclones. Two of the clones had an active suppressor gene (sup+ clones) and two of them had lost the suppressor (sup- clones) yet remained anchorage dependent. Both sup+ and sup- clones could be transformed to anchorage independence by ras, src, mos, neu, polyoma mT and SV40 suggesting that neither the presence nor the absence of the suppressor gene in BHK limits the transforming ability of these common oncogenes. All lines were resistant to transformation by N-myc, E1A and c-sis, oncogenes that may perform redundant functions in the immortal, fast growing BHK cell. SV40 small t antigen which has previously been considered unable to transform cultured cells by itself, was nevertheless able to transform sup+ BHK lines to anchorage independence in the absence of the viral large T antigen. Clones of sup- cells expressing high levels of small t antigen protein could be isolated, but they remained anchorage dependent and in tumorigenicity assays retained the long latent period characteristic of normal BHK cells. Such lines should enable the identification of cellular targets vital to the transforming function of SV40 small t.
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PMID:Influence of a hamster tumor suppressor gene on transformation by viral and cellular oncogenes. 838 73

The activation of oncogenes and inactivation of tumor suppressor genes (TSGs) have been implicated in the development of many human and animal malignancies. Changes in certain specific genes have been shown to be of potential value for diagnosis and prognosis, as well as treatment, of some cancers. By contrast, no oncogene has been correlated conclusively at the DNA level with the initiation and progression of prostate cancer, although though there are alterations in expression of a number of oncogenes (i.e., ras, c-sis, c-fos, and neu) in messenger RNA and/or protein level. It is also thought that alterations of certain known TSGs, such as p53, KAII, and E-cadherin, may be important in prostate carcinogenesis; alterations of KAII (known as a metastasis suppressor gene) and p53 are more likely to be associated with the late events in the development of prostate cancers. Other TSGs, such as Rb, nm23, and PACI, require more studies to further define their role. The possible presence of TSGs in frequently altered regions on chromosomes 6q14-21, 8q, 10p, 10q, 13q, and 17p have been actively studied. Moreover, further studies on other frequently altered regions on chromosomes 2q, 5q, 15q, 16q, l7q, and 18q may provide further insight into the mechanism of prostate cancer progression. Future studies should be targeted on these putative oncogenes and TSGs and to determine whether assessment of specific gains or losses may have prognostic value in the diagnosis and treatment of prostate cancer.
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PMID:Oncogenes and tumor suppressor genes in prostate cancer: a review. 2122 58