Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C1326912 (tumorigenesis)
 57,481 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Stomatin-like protein 2 (SLP-2) is a novel and unusual stomatin homologue of unknown functions. It was first identified to be overexpressed and involved in regulating cell growth and cell adhesion in human esophageal squamous cell carcinoma. We show herein the involvement of SLP-2 in human endometrial adenocarcinoma, and the effects of SLP-2 on endometrial adenocarcinoma cell growth. The expression of SLP-2 was evaluated in human endometrial adenocarcinoma by semi-quantitative RT-PCR, Westernblotting and immunohistochemistry. Sense and antisense SLP-2 eukaryotic expression plasmids were transfected into the human endometrial adenocarcinoma cell line HEC-1B. MTT assay and flow cytometry assay were performed to investigate the roles of the SLP-2 gene. SLP-2 was overexpressed in endometrial adenocarcinoma compared with their normal counterparts (P<or=0.05). Immunohistochemistry showed that SLP-2 was mainly localized in the cytoplasm with some distribution on the membrane. HEC-1B cells transfected with antisense SLP-2 showed decreased cell growth, whereas the cell growth increased with the sense transfection. SLP-2 was first identified as a novel cancer-related gene overexpressed in human endometrial adenocarcinoma. Cell growth changes with the sense and antisense transfection revealed that SLP-2 might be important in endometrial tumorigenesis.
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PMID:Stomatin-like protein 2 is overexpressed and related to cell growth in human endometrial adenocarcinoma. 1734 23

Bcl-XL is overexpressed in a variety of human tumors and is involved in tumorigenesis and chemoresistance. This study investigated the inhibitory effect of the hairpin Bcl-XL small interfering RNA (siRNA) on the expression of the Bcl-XL gene in the cisplatin (DDP)-resistant human lung adenocarcinoma cell line A549/DDP, and the effect of Bcl-XL siRNA on drug sensitization in A549/DDP cells. Bcl-XL siRNA and negative siRNA plasmids were constructed and stably transfected into A549/DDP cells. Reverse transcription-polymerase chain reaction and Western blot analysis were used to detect the target gene expression. Spontaneous apoptosis of cells was detected by acridine orange and ethidium bromide staining. Drug sensitivity of the cells to DDP was analyzed with dimethylthiazol-diphenyltetrazolium bromide (MTT) and flow cytometry. Expression levels of Bcl-XL mRNA and protein in siRNA stable transfectants were clearly reduced as compared with negative siRNA transfectants and untreated cells. MTT results indicated that Bcl-XL transfectants had a higher cell inhibition rate than the negative vector or untreated cells after treatment with 0.2-200 micarog/ml DDP. Flow cytometry revealed increased apoptosis in Bcl-XL siRNA cells. After the addition of 20 microg/ml DDP, siRNA targeting of the Bcl-XL gene specifically down-regulated gene expression in A549/DDP cells, increased spontaneous apoptosis, and sensitized cells to DDP. The results showed that Bcl-XL siRNA contributed to an increase of DDP-induced cell death in non-small-cell lung cancer and sensitized cells to DDP, leading to increased the effectiveness of the drug in treating non-small-cell lung cancer.
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PMID:Bcl-XL small interfering RNA sensitizes cisplatin-resistant human lung adenocarcinoma cells. 1749 31

Our previous studies have found that reducing expression of myeloid zinc finger-1 (MZF-1) inhibited protein kinase C alpha (PKCalpha) expression and decreased cell migration and invasion in human hepatocellular carcinoma (HCC). In this study, we further investigated the role of MZF-1 in tumorigenesis. The SK-Hep-1 HCC cells were transfected with the antisense oligonucleotide (ODN) of MZF-1. The pretreated cells was then detected the mRNA and protein levels by RT-PCR and western blotting, and the cell growth was assayed by MTT. Meanwhile, the pretreated-SK-Hep-1 HCC cells were implanted subcutaneously into nude mice to observe the tumor growth and calculated tumor inhibitory rate. The results showed that, at the dosage of 5 microM, the antisense ODN MZF-1 suppressed both MZF-1 and PKCalpha productions by SK-Hep-1 HCC cells after cationic liposome-mediated transfection, to 15% and 30% in control cultures of 0 microM dosage, respectively. The growth of SK-Hep-1 HCC cells was inhibited by the 2-5 microM doses of the antisense ODN MZF-1, whereas the control reagent, the sense ODN MZF-1, showed no effects. In BALB/nude mice, SK-Hep-1 HCC cells pretreated with the 5 microM antisense ODN MZF-1 formed tumors much smaller than the cells with sense ODN. The mean of inhibitory rate of tumor growth was 71.2 +/- 8.6%, and the tumor formation time was prolonged from 14 days to 26 days. These findings suggested the usefulness of antisense ODN MZF-1 as a new reagent for cancer therapy.
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PMID:Suppression of tumorigenicity of human hepatocellular carcinoma cells by antisense oligonucleotide MZF-1. 1759 97

Introduction of human chromosome 6 into malignant melanoma cell line UACC903 resulted in generation of the chromosome 6-mediated suppressed cell subline UACC903(+6) that displays attenuated growth rate, anchorage-dependency, and reduced tumorigenicity. We have showed that overexpression of a chromosome 6-encoded tumor suppressor gene led to partial suppression to UACC903 cell growth. We now describe the differences in apoptosis and cell cycle between UACC903 and UACC903(+6) before and after UV irradiation. MTT assay revealed 86.92+/-8.24% of UACC903 cells viable, significantly (p<0.01) higher than 48.76+/-5.31% of UACC903(+6), at 24 hr after 254-nm UV irradiation (40 J/M(2)). Before UV treatment, flow cytometry analysis revealed 6.06+/-0.20% apoptosis in UACC903, significantly (p=0.01) lower than 6.67+/-0.15% in UACC903(+6). The G0/G1, S and G2/M phase cells of UACC903 were, respectively, 54.10+/-0.59%, 22.31+/-0.50% and 16.85+/-0.25%, all significantly (p<0.01) different from the corresponding percentages (58.82+/-0.35%, 20.48+/-0.05%, and 13.17+/-0.45%) of UACC903(+6). After the UV treatment, UACC903 cells in apoptosis, G0/G1, S, and G2/M became 12.59+/-0.17%, 38.90+/-0.67%, 19.74+/-0.70%, and 27.01+/-0.66%, respectively, while UACC903(+6) cells were 24.16+/-0.48%, 37.97+/-0.62%, 19.20+/-0.52%, and 15.69+/-0.14%. TUNEL assay revealed 2.31+/-0.62% apoptosis in UACC903, significantly (p<0.01) lower than 9.60+/-1.14% of UACC903(+6), and a linear and exponential increase of apoptosis, respectively, in response to the UV treatment. These results indicate that UACC903(+6) cells have a greater tendency to undergo apoptosis and are thus much more sensitive to UV irradiation. Our findings further suggest a novel mechanism for chromosome 6-mediated suppression of tumorigenesis and metastasis, i.e., through increased cell death.
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PMID:Differences in apoptosis and cell cycle distribution between human melanoma cell lines UACC903 and UACC903(+6), before and after UV irradiation. 1765 83

In previous studies, we showed that reducing Ets-like protein-1 (Elk-1) expression inhibited protein kinase C alpha (PKC alpha) expression and decreased cell migration and invasion in human hepatocellular carcinoma (HCC). In this study, we have investigated the role of Elk-1 in tumorigenesis. SK-Hep-1 HCC cells were transfected with the ElK-1 antisense oligonucleotide (ODN). In the pretreated cells we detected a reduction of mRNA level using RT-PCR. The inhibitory rate of cell growth was measured by MTT assay. Pretreated-SK-Hep-1 HCC cells were implanted subcutaneously into nude mice to observe the tumor growth and calculate tumor inhibitory rate. The results showed that 5 microM of the antisense ODN Elk-1 suppressed both Elk-1 and PKC alpha production by SK-Hep-1 HCC cells after cationic liposome-mediated transfection, to 8% and 1% of control values, respectively, and the growth of SK-Hep-1 HCC cells was inhibited at 2-5 microM doses of the antisense ODN Elk-1. The control reagent, sense ODN Elk-1, showed no effects. In BALB/nude mice, SK-Hep-1 HCC cells transfected with the 5 microM antisense ODN Elk-1 formed tumors much smaller than those of sense ODN Elk-1 pretreated cells. The maximum inhibitory rate of tumor growth was 80.8+/-12.6% and the tumor formation time was prolonged from 13 to 25 days. These findings suggested the usefulness of antisense ODN Elk-1 as a new reagent for liver cancer therapy.
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PMID:Antisense oligonucleotide Elk-1 suppresses the tumorigenicity of human hepatocellular carcinoma cells. 1795 2

Bcl-2 is overexpressed in a variety of human tumors and is involved in tumorigenesis and chemoresistance. In this study, we investigated the inhibitory effect of the hairpin Bcl-2 small interfering (si)RNA on the expression of the Bcl-2 gene in the cisplatin (DDP)-resistant human lung adenocarcinoma cell line A549/DDP, and the effect of Bcl-2 siRNA on drug sensitization in A549/DDP cells. Bcl-2 siRNA and negative siRNA plasmids were constructed and stably transfected into A549/DDP cells. Reverse transcription-polymerase chain reaction, immunofluorescence microscopy and Western blot analysis were used to detect the target gene expression. Spontaneous cell apoptosis was detected by acridine orange and ethidium bromide staining. Drug sensitivity of the cells to DDP and diallyl disulfide (DADS) was analyzed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry. Expression levels of Bcl-2 mRNA and protein in siRNA stable transfectants were clearly reduced compared with negative siRNA transfectants and untreated cells. MTT results indicated that Bcl-2 transfectants had a higher cell inhibition rate after treatment with 0.2-200 microg/ml DDP or 50-200 microM DADS. Flow cytometry revealed increased apoptosis in Bcl-2 siRNA cells. After the addition of 20 microg/ml DDP or 100 microM DADS, siRNA targeting of the Bcl-2 gene specifically down-regulated gene expression in A549/DDP cells, increased spontaneous apoptosis, and sensitized cells to DDP and DADS.
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PMID:Bcl-2 small interfering RNA sensitizes cisplatin-resistant human lung adenocarcinoma A549/DDP cell to cisplatin and diallyl disulfide. 1798 74

Peroxisome proliferator-activated receptor-gamma (PPAR)-gamma is a ligand-activated transcriptional factor belonging to steroid receptor superfamily. PPAR-gamma plays a role in both adipocyte differentiation and tumorigenesis. Up to date, PPAR-gamma is expressed in various cancer tissues, and PPAR-gamma ligand induces growth arrest of these cancer cells. In this study, we examined the expression of PPAR-gamma in prostate cancer (PC) and testicular cancer (TC) by RT-PCR and immunohistochemistry, and we also examined the effect of PPAR-gamma ligand in these cells by MTT assay, hoechest staining, and flow cytometry. PPAR-gamma expression was significantly more extensive and intense in malignant tissues than in normal tissues. PPAR-gamma ligand induced the reduction of malignant cell viability through apoptosis. These results demonstrated that the generated PPAR-gamma in PC and TC cells might play an important role in the tumorigenesis. PPAR-gamma may become a new target in the treatment of PC and TC.
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PMID:Peroxisome Proliferator-Activated Receptor-gamma Is a Potent Target for Prevention and Treatment in Human Prostate and Testicular Cancer. 1831 13

To investigate the effects of Ku80 depletion on cell growth and sensitization to gamma-radiation and MMC-induced apoptosis in esophageal squamous cell carcinoma lines. Six human carcinoma cell lines (LNcaP, K562, MDA-MB-231, MCF-7, EC9706, and K150) and normal HEK293 cell line were examined for basal levels of Ku80 protein by western blotting analysis. The suppression of Ku80 expression was performed using vector-based shRNA in EC9706 cells. Cell proliferation was determined with MTT assay and colony formation assay and tumorigenicity in a xenograft model in vitro and in vivo. Sensitivity of EC9706 cells treated with shRNA vector to gamma-radiation and MMC was determined with colony formation assay and MTT assay. The cell cycle distribution was determined by Flow cytometry. Apoptosis induced by gamma-radiation and MMC was analyzed using GENMED-TUNEL FACS kit. Ku80 showed higher basal levels in six carcinoma cell lines than in HEK293. The suppression of Ku80 expression decreased cellular proliferation, colony formation and inhibited tumorigenicity in a xenograft model. Furthermore, it sensitized apoptosis of the cancer cells induced by gamma-radiation and MMC. Ku80 plays an important role not only in tumorigenesis but also in radiation resistance and chemotherapy resistance in esophageal cancer cells. Hence Ku80 may serve as a promising therapeutic target, particularly for recurrent esophageal tumors.
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PMID:ShRNA-mediated Ku80 gene silencing inhibits cell proliferation and sensitizes to gamma-radiation and mitomycin C-induced apoptosis in esophageal squamous cell carcinoma lines. 1840 3

Chronic exposure to solar UV irradiation leads to photoaging, immunosuppression, and ultimately carcinogenesis. Cellular senescence is thought to play an important role in tumor suppression and apoptosis resistance. However, the relationships among stress-induced premature senescence (SIPS), tumorigenesis and apoptosis induced by UVB remain unknown. We developed a model of UVB-induced premature senescence in human skin fibroblasts (HSFs). After five repeated subcytotoxic UVB exposures at a dose of 10 mJ/cm2, the following biomarkers of senescence were markedly present: senescence-associated beta-galactosidase (SA beta-gal) activity, growth arrest, and the overexpression of senescence-associated genes. Firstly, there was an increase in the proportion of cells positive for SA beta-gal activity. Secondly, there was a loss of replicative potential as assessed by MTT assay. FACS analysis showed that UVB-stressed HSFs were blocked mostly in the G1 phase of the cell cycle, and replicative senescence, and protein expression of p53, p21(WAF-1) and p16(INK-4a) increased significantly. Thirdly, the mRNA levels of three senescence-associated genes, fibronectin, osteonectin and SM22, also increased. A real time PCR array to investigate the mRNA expression of p53-related genes involved in growth arrest, apoptosis and tumorigenesis indicated that p53, p21, p19, Hdm2, and Bax were up-regulated, and bcl, HIF-1alpha and VEGF were down-regulated. Collectively, our data suggest that UVB-induced SIPS plays an important role in p53-related apoptosis resistance and tumor suppression activity.
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PMID:p53-related apoptosis resistance and tumor suppression activity in UVB-induced premature senescent human skin fibroblasts. 1842 58

The initiation and progression of tumor is regulated by multiple genes. Survivin belongs to the inhibitor of apoptosis protein (IAP) family and is overexpressed in most types of human tumors. Apoptin, originally identified from chicken anemia virus (CAV), can specifically induce apoptosis of human tumor cells rather than normal cells. In this study, survivin expression was silenced by microRNA (miRNA)-mediated RNA interference (RNAi); meanwhile, the engineered miRNA vector was also designed to express apoptin gene. The apoptosis and cell growth were then examined by flow cytometry and MTT assay. The miRNA-mediated knockdown of survivin in combination with apoptin overexpression significantly induced apoptosis and inhibited cell growth. Importantly, the combined strategy was more effective on inducing apoptosis and inhibiting cell growth than either survivin downregulation or apoptin overexpression alone. Taken together, the combined strategy offers potential advantages in control of tumorigenesis, and thus deserves further research as a preferred approach in cancer gene therapy.
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PMID:Survivin knockdown combined with apoptin overexpression inhibits cell growth significantly. 1869 66


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