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)

Mechanisms involved in cellular radioresistance are mostly unknown and may be related to specific genetic alterations. In order to correlate the most frequent oncogenic alterations detected in tumors and ionizing radiation resistance, we studied the effect of irradiation on murine keratinocytes transformed by different oncogenes. Mouse PAM 212 keratinocytes were transformed by transfection or retroviral mediated infection with the oncogenes v-H-ras, v-myc, adenovirus Ela, neu and a mutant p53 (mp53). Cells were gamma irradiated with a Co-60 source. Cell viability was evaluated by the crystal violet method and thymidine uptake and data adjusted to the linear-quadratic model. Surviving fraction 2Gy (SF2) and DO was calculated. Cell cycle study was assessed by incorporation of bromodeoxyridine (BrdUrd) and flow cytometry. p53 protein was studied by Western-blot and apoptosis in DNA agarose gels. The surviving fraction for the different keratinocytes, PAM 212, 212 neo, 212 Ela, 212 v-H-ras, 212 myc, 212 neu and 212 mp53 was 0.79, 0.78, 0.34, 0.82, 0.68, 0.74, and 0.72, respectively. Ela oncogene induced a great sensitivity to irradiation and v-H-ras a mild radioresistance. In flow cytometry, 212 Ela keratinocytes displayed a pronounced and prolonged arrest in G2/M phase. Apoptosis was observed after irradiation only in the 212 Ela keratinocytes. With these results, we conclude that some oncogene products may modulate radiosensitivity in keratinocytes. Mechanisms involved in radiosensitivity mediated by the Ela oncogene seem to be related to p53 protein level, induction of apoptosis and to an irreversible premitotic arrest in G2/M phase, ineffective for repair of DNA damage.
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PMID:Oncogenes and cellular-sensitivity to radiotherapy - a study on murine keratinocytes transformed by v-h-ras, v-myc, v-Neu, adenovirus e1a and mutant p53. 2155 21

Recent work has shown that HER2/neu-positive breast cancer cells rely on a unique Warburg-like metabolism for survival and aggressive behavior. These cells are dependent on fatty acid (FA) synthesis, show markedly increased levels of stored fats and disruption of the synthetic process results in apoptosis. In this study, we used global metabolite profiling and a multi-omics network analysis approach to model the metabolic changes in this physiology under palmitate-supplemented growth conditions to gain insights into the molecular mechanism and its relevance to disease prevention and treatment. Computational analyses were used to define pathway enrichment based on the dataset of significantly altered metabolites and to integrate metabolomics and transcriptomics data in a multi-omics network analysis. Network-predicted changes and functional relationships were tested with cell assays in vitro. Palmitate-supplemented growth conditions induce distinct metabolic alterations. Growth of HER2-normal MCF7 cells is unaffected under these conditions whereas HER2/neu-positive cells display unchanged neutral lipid content, AMPK activation, inhibition of fatty acid synthesis and significantly altered glutamine, glucose and serine/glycine metabolism. The predominant upregulated lipid species is the novel bioactive lipid N-palmitoylglycine, which is non-toxic to these cells. Limiting the availability of glutamine significantly ameliorates the lipotoxic effects of palmitate, reduces CHOP and XBP1(s) induction and restores the expression levels of HER2 and HER3. The study shows that HER2/neu-positive breast cancer cells change their metabolic phenotype in the presence of palmitate. Palmitate induces AMPK activation and inhibition of fatty acid synthesis that feeds back into glycolysis as well as anaplerotic glutamine metabolism.
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PMID:Global metabolite profiling analysis of lipotoxicity in HER2/neu-positive breast cancer cells. 2993 Jul 56