Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:EXPT01586 (G418)
 2,237 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neonatal rat hepatocytes (NRH) in primary cultures were transformed upon transfection with plasmid pSV 5-neo containing polyoma virus (Py) early region sequences. Clones of cells (Py-NRH) resistant to the antibiotic G418 were obtained after selection in arginine-deficient medium with serum, epidermal growth factor (EGF), transferrin and insulin. They did not undergo senescence during serial subcultivation. One clone (Py-NRH Cl A) harbored a single integrated copy of Py early region sequences and expressed transforming Py genes, hepatocyte-specific transcripts, including albumin, alpha-fetoprotein (AFP) and tyrosine aminotransferase (TAT) mRNAs. Subclones isolated after about 45 cell doublings still contained albumin and AFP, but no TAT mRNAs, indicating that long-term stabilization of liver functions is not necessarily permanent unless selected for (e.g. arginine synthesis). Cells grew unrestricted in medium containing insulin and no longer required EGF. Cells grew in agar, secreted a beta-transforming growth factor-like activity into the medium and were tumorigenic in nude mice. Hybridization studies using v-erbB DNA as a probe showed that Py-NRH, unlike neonatal hepatocytes in primary culture, express the EGF receptor gene at low or undetectable levels. Py-NRH Cl A and a subclone (5A) derived from it, however, contained elevated levels of rat c-neu oncogene-related RNA, whereas levels in another subclone (3A) were low or undetectable. These findings demonstrate that a proto-oncogene was activated after transfection of hepatocytes with DNA tumor virus transforming genes. However, the expression of c-neu oncogene is not related to the maintenance of the transformed state.
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PMID:Transformation of differentiated neonatal rat hepatocytes in primary culture by polyoma virus early region sequences. 283 82

Overexpression of p185erbB2/neu has been detected in many adenocarcinomas, including prostatic cancer. In this study, a nontumorigenic cell line isolated from the rat prostatic epithelium (NbE) transfected with the activated oncogene p185neu-T was used to investigate the role of this oncogene in tumor progression. When clones overexpressing p185neu-T were injected orthotopically (1.5 to 2 x 10(6) cells) into the dorsal-lateral prostates of nude mice, prostatic tumors were detected in all mice injected and metastasis to the skeletal muscle in the rib area in 60-80% of the mice injected. Tumor and metastasis origin was confirmed by reselection with G418 and reverse transcriptase-polymerase chain reaction. Control cell lines produced no prostatic tumors or metastases. Incubation at low density (12500 cells/2 cm2) in serum-free medium revealed that clones overexpressing p185neu-T had a higher rate of [3H]thymidine incorporation than did control clones on 3, 5, and 7 d after plating (P < or = 0.0001) and constitutively overexpressed the 2.6-kb ornithine decarboxylase transcript. Additionally, clones overexpressing p185neu-T demonstrated an increased expression of epidermal growth factor receptor and p180erbB4, as judged by RNA blot analysis. Together these data support the hypothesis that overexpression of p185neu-T fosters tumor progression by several pathways, including induction of the metastatic cascade, increased proliferative capabilities, and increased expression of other members of the erbB2 gene family.
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PMID:Metastasis induced by overexpression of p185neu-T after orthotopic injection into a prostatic epithelial cell line (NbE). 925 83

Genomic alterations in primary breast cancer play a role in the initiation and progression of the disease. We have analyzed the molecular events involved in the initiation and progression of the neoplastic process in an in vitro experimental system. Immortalization of human breast epithelial cells (HBEC) is associated with 3:9 translocation, p53 mutation and microsatellite instability (MSI) of chromosomes 11p13, and 17p. BP1-E cells, derived from the immortalized MCF-10F cells transformed by the carcinogen benzo(a)pyrene (BP), express in vitro growth advantage, anchorage independence, enhanced chemoinvasiveness, loss of ductulogenic capabilities and tumorigenesis in a heterologous host. This neoplastic progression is also associated with mutations and/or amplification of c-H-ras, int-2, c-neu, c-myc and MDM2, MSI at 11q25 and 13q12-q13 and loss of heterozygosity at 17p. In order to test whether chromosomes 11 or 17 play a functional role in the phenotypic expression of transformation of BP1E cells, we utilized microcell-mediated chromosome transfer (MMCT) technique for inserting the corresponding normal chromosomes to these transformed cells. BP1E cells were transfected with PsV2neo plasmid and fused with microcells obtained from the mouse cell line A9, containing a normal chromosome 11 or 17 (A9-11neo and A9-17neo cells, selected in G418 and cloned. Sixteen primary microcell hybrids from each chromosome transfer, designated BP1E-11neo and BP1E-17neo survived selection in G-418 containing medium. A single clone from each group, BP1E-11neo #145 and BP1E-17neo D100, survived subcloning and were utilized for a detailed panel of analyses. The presence of a donor chromosome was confirmed by dual color fluorescence in situ hybridization (FISH), southern blot analysis of the marker vector pSV2neo, and microsatellite polymorphism analysis. The transfer of the normal chromosomes 11 and 17 resulted in a 50% and 90% inhibition of cell growth respectively, and reduced both colony efficiency and colony size. Telomerase activity was significantly reduced only by chromosome 17 insertion, providing a possible explanation for the more significant senescence observed in BP1E-17neo D100 cells. Microsatellite polymorphism analysis revealed that three loci, 11q13-23, 11q23.1, and 11q23.3 (markers D11S911, DRD2, and D11S29) were retained in BP1E-11neo #145 cells, and two, 17q24.2-25.2, 17q25.2 (markers D17S515 and D17S785 were retained in BP1E-17neo D100 cells. We conclude that the specific regions of normal chromosomes 11 and 17 transferred play a functional role in the expression of immortal and transformed phenotypes of HBEC in vitro.
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PMID:Functional roles of chromosomes 11 and 17 in the transformation of human breast epithelial cells in vitro. 1049 42