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)

A series of functional studies were performed to assess the potential role of the ras-related transformation suppressor gene, Krev-1, in suppressing prostate cancer cell growth. Three human prostate cancer cell lines, PC-3, TSU-Pr1, and DU-145 were transfected with a plasmid containing the Krev-1 cDNA and a neomycin resistance gene. Selected G418-resistant clones were isolated and expanded into cell lines. All cloned transfectants exhibited a significant reduction in their in vitro growth rates, i.e., longer doubling times, when compared to the parental cell lines. Molecular analysis of the Krev-1 cloned transfectants revealed that they all contained variable copy numbers of the Krev-1 gene and expressed high levels of Krev-1 mRNA transcript, as shown by Southern and Northern analysis, respectively. To determine whether the biological properties associated with tumorigenicity were changed in these Krev-1 transfectants, their growth characteristics were examined on the basis of their ability to a) form colonies in soft agar, and b) produce tumors in SCID mice. The majority of the Krev-1 transfectants from the PC-3 and TSU-Pr1 cell lines showed a substantially reduced ability to form colonies in soft agar and produced significantly smaller tumors when inoculated into SCID mice. In contrast, there was no significant reduction in the soft agar colony-forming ability or in vivo tumorigenicity of the DU-145 Krev-1 transfectants. These results suggest that the Krev-1 suppressor gene induces partial suppression of the malignant phenotype of human prostate cancer cells containing activated ras oncogenes.
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PMID:Partial growth suppression of human prostate cancer cells by the Krev-1 suppressor gene. 808 35

Here, we report a fluorescent spontaneous bone metastatic model of human prostate cancer developed by surgical orthotopic implantation of green fluorescent protein (GFP)-expressing prostate cancer tissue. Human prostate cancer PC-3 cells were transduced with the pLEIN expression retroviral vector containing the enhanced GFP and neomycin resistance genes. Stable GFP high-expression PC-3 clones were selected in vitro with G418, which were then combined and injected s.c. in nude mice. For metastasis studies, fragments of a single highly fluorescent s.c. growing tumor were implanted by surgical orthotopic implantation in the prostate of a series of nude mice. Subsequent micrometastases and metastases were visualized by GFP fluorescence throughout the skeleton, including the skull, rib, pelvis, femur, and tibia The central nervous system, including the brain and spinal cord, was also involved with tumor, as visualized by GFP fluorescence. Systemic organs, including the lung, plural membrane, liver, kidney, and adrenal gland, also had fluorescent metastases. The metastasis pattern in this model reflects the bone and other metastatic sites of human prostate cancer. Thus, this model should be very useful for the study and development of treatment for metastatic androgen-independent prostate cancer.
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PMID:A fluorescent orthotopic bone metastasis model of human prostate cancer. 1002 62

The expression and activation of matrix metalloproteinases (MMPs) by tumor cells is correlated with progression to invasive and metastatic status. The purpose of this study was to examine the role of increased MMP-2 (gelatinase A) expression in prostate cancer progression utilizing human prostate PC-3 cancer cells that overexpress MMP-2 using gene transfection. PC-3 cells were transfected with pCR-3 vector only and pCR-3 MMP-2 plasmids employing the LipofectAMINE method, and stable transfectants were selected with G418. The expression of MMP-2, tissue inhibitor of metalloproteinase-2 (TIMP-2), and membrane-type MMP 1 (MT1-MMP) in PC-3 parental and transfected cells under serum-free conditions was determined by zymography, immunoblotting, immunofluorescent microscopy, Northern blotting, and/or reverse transcriptase-polymerase chain reaction (RT-PCR). MMP-2 transfected cells produced primarily the proenzyme form of MMP-2; the parental and vector control transfected PC-3 cells did not express any MMP-2 that was detectable by the methods we employed. Treatment of PC-3 MMP-2 transfected cells with Concanavalin A (Con A), in contrast to HT-1080 cells, processed only a small amount of the secreted 72-kd proenzyme to a 62-kd intermediate and a cell-associated 59-kd active form. The low level of secreted pro-MMP-2 processing induced by Con A was inhibited by serine protease inhibitors and was unaffected by cyclic adenosine monophosphate (cAMP). Immunoblotting showed that these cells produced abundant TIMP-2 and lower amounts of MT1-MMP in comparison with Con A-responding HT-1080 cells. HT-1080 cells respond to Con A by translocating MT1-MMP from intracellular localization sites to the plasma membrane, an effect not observed in PC-3 cells. The molecular basis for the low level of processing of pro-MMP-2 by PC-3 cells may be due to an overabundance of TIMP-2 and/or a low level of cell surface active MT1-MMP.
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PMID:Limited processing of pro-matrix metalloprotease-2 (gelatinase A) overexpressed by transfection in PC-3 human prostate tumor cells: association with restricted cell surface localization of membrane-type matrix metalloproteinase-1. 1476 14