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)

Neoplastic development of Syrian hamster embryo (SHE) cells in culture is a multistep process in which intermediate or preneoplastic cells can be identified and isolated. In an attempt to further characterize normal and preneoplastic cells, we have compared their susceptibilities to neoplastic transformation following transfection with cloned DNA of the oncogenic virus, Harvey murine sarcoma virus (HaMSV). Normal SHE cells, which are stably nontumorigenic when injected in nude mice, are competent to take up and express exogenous DNA as demonstrated by transfection experiments with pSV2-neo DNA and certain viral DNAs. SHE cells treated with 5 micrograms of HaMSV DNA per dish remained nontumorigenic. Colonies of SHE cells, isolated after cotransfection with HaMSV and pSV2-neo DNA and selection for G418 antibiotic resistance, expressed Harvey murine sarcoma virus oncogene (v-Ha-ras) RNA and were initially morphologically altered; however, all colonies senesced when subcultured. In contrast, transfection of the cells with polyoma virus DNA alone or HaMSV DNA plus MC29 viral DNA (pSVv-myc) and then injection of the cells into nude mice resulted in progressively growing tumors of hamster origin within 3 to 5 weeks. A preneoplastic cell line, DES-4, isolated after treatment of SHE cells with the human carcinogen diethylstilbestrol, was chosen for comparative analyses. These immortalized cells are nontumorigenic and excellent recipients for exogenous DNA. In contrast to SHE cells, DES-4 cells were highly susceptible to neoplastic transformation following transfection with HaMSV DNA. To further investigate the role of HaMSV DNA in the neoplastic transformation of DES-4 cells and to determine whether this occurred as a single step, clones of DES-4 cells cotransfected with pSV2-neo and HaMSV DNAs were selected by antibiotic resistance and characterized. There was a good correlation between tumorigenicity and expression of v-Ha-ras DNA; however, the clones were highly variable in terms of their latency periods in vivo and anchorage-independent growth. Neither of these two parameters correlated with the level of expression of v-Ha-ras RNA. All of the cell lines derived from tumors and reinoculated into nude mice had short latency periods in vivo, were highly anchorage independent, and had high levels of v-Ha-ras expression. These results suggest that, in these experiments, v-Ha-ras expression was necessary, but not sufficient, for the tumorigenicity of DES-4 cells and that additional changes in the cells were acquired.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Evidence for multiple steps in neoplastic transformation of normal and preneoplastic Syrian hamster embryo cells following transfection with Harvey murine sarcoma virus oncogene (v-Ha-ras). 298 12

Estrogen receptor-related receptor alpha (ERRalpha) was reported to compete with estrogen receptor alpha (ERalpha) in a constitutive manner as an orphan nuclear closely related to (ERalpha). To discuss the role of ERRalpha in the endometrial carcinoma cells, this study was performed. ER-responsive endometrial carcinoma cells Ishikawa and ER-nonresponse HEC-1A cells were treated with different concentration of 17beta-E2 or E2 plus ICI 182780. Semiquantitative reverse transcription-polymerase chain reaction and western blot were performed to analysis the expression of human estrogen receptor-related receptor alpha (hERRalpha). Plasmid PLXSN-hERRalpha was constructed and transfected into cells. Selected in the medium containing high-dose G418, the Ishikawa and HEC-1A cells with stable overexpression of hERRalpha were constructed and renamed as Ishikawa/hERRalpha and HEC-1A/hERRalpha, respectively. To discuss the effect of overexpression of hERRalpha in the cell biological behavior (3-[4,5-dimethylth-lazol-2yl]-2,5-diphenyltetrazolium bromid) (MTT) cell assay was performed. Estrogen downregulates ERRalpha expression in ER-positive Ishikawa cells, while upregulates the expression of ERRalpha in ER-negative HEC-1A cells. In Ishikawa cells, the downregulation of 17beta-E2 in ERRalpha expression cells could be blocked by ICI 182780. A decreasing expression of hERalpha was observed in the ER-responsive cells with overexpression of ERRalpha (Ishikawa/hERRalpha). Overexpression of hERRalpha inhibits the cell proliferation in the ERalpha-responsive Ishikawa cells and stimulated the cell proliferation in the ERalpha-nonresponsive HEC-1A cells. Function of hERRalpha depends on the expression and function of hERalpha. ER-mediated signaling might be the important factor resulting in the hormone-dependent endometrial carcinoma, whereas ERRalpha-mediated pathway might act as the vital role in hormone-independent endometrial carcinoma.
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PMID:An estrogen receptor alpha-dependent regulation of estrogen receptor-related receptor alpha in the proliferation of endometrial carcinoma cells. 1701 74