Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

(+/-)-13-Hydroxy-10-oxo-trans-11-octadecenoic acid (13-HOA) is one of the lipoxygenase metabolites of linoleic acid (LA) from corn germ. Recently, we reported that this metabolite suppressed the expression of lipopolysaccharide-induced proinflammatory genes in murine macrophages by disrupting mitogen-activated protein kinases and Akt pathways. In this study, we investigated the inhibitory effects of 13-HOA on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation in ears and skin, as well as tumor promotion in female ICR mice. Pretreatment with 13-HOA (1600 nmol) inhibited ear edema formation by 95% (P < 0.05) in an inflammation test and reduced tumor incidence and the number of tumors per mouse by 40 and 64% (P < 0.05 each), respectively, in a two-stage skin carcinogenesis model. Histological examinations revealed that it decreased epidermal thickness, the number of infiltrated leukocytes and cell proliferation index. Furthermore, 13-HOA (8-40 muM) suppressed TPA-induced anchorage-independent growth of JB6 mouse epidermal cells by 70-100%, whereas LA was virtually inactive. 13-HOA (40 muM) inhibited TPA-induced activator protein-1 transactivation but not extracellular signal-regulated kinase1/2 activation. Interestingly, 13-HOA (40 muM and 1600 nmol in JB6 cells and mouse skin, respectively) induced expression of programmed cell death 4 (Pdcd4), a novel tumor suppressor protein. To our knowledge, this is the first report of a food factor that is able to induce Pdcd4 expression. Collectively, our results indicate that 13-HOA may be a novel anti-inflammatory and antitumor chemopreventive agent with a unique mode of action.
Carcinogenesis 2009 Jul
PMID:Linoleic acid metabolite suppresses skin inflammation and tumor promotion in mice: possible roles of programmed cell death 4 induction. 1941 3

Molecular insights into the human papillomavirus (HPV)-induced cervical carcinogenesis led to the discovery of biomarkers for cervical disease. The detection of cellular proteins that are overexpressed by HPV-infected cells, such as tumor suppressor protein p16(INK4a), might play an important role in future cervical cancer screening strategies. P16(INK4a) immunostaining correlates with the severity of cytological and histological abnormalities, but shows some methodological shortcomings such as the lack of standardized methodology and interobserver variability. This study evaluated quantitative reverse transcriptase PCR (RT-PCR) as an alternative tool to analyze p16(INK4a) overexpression as a biomarker for transforming HPV-infections in a liquid-based cervical cytology (LBC) setting. Sixty LBC samples, divided in three groups based on their cytological diagnosis, were subjected to HPV typing and analysis of p16 expression by immunocytochemistry and RT-PCR. The analytical sensitivity of the RT-PCR was determined by spiking HeLa and HaCaT cells. P16(INK4a) expression measured by RT-PCR did not correlate with the cytological diagnosis or HPV status (HPV-positivity, infection type and HPV16-positivity). The spiking experiment proved that, to detect increased biomarker expression by RT-PCR, about 1.0% dysplastic cells is required within a pool of normal keratinocytes. In conclusion, RT-PCR analysis of biomarker expression is not appropriate for cervical screening purposes. In typical LBC samples, the biomarker transcripts of the dysplastic cells are diluted by the RNA of the normal cells in such a manner that their overexpression cannot be detected by RT-PCR.
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PMID:Biomarkers in cervical screening: quantitative reverse transcriptase PCR analysis of P16INK4a expression. 1991 Jul 96

It has been reported that Rho and Rho-kinase are involved in actin cytoskeleton organization and associated with carcinogenesis and progression of human cancers. However, the mechanism how the Rho/Rho-kinase pathway is involved in cell cycle progression has not been precisely characterized. In this study, we investigated the role of Rho-kinase in epidermal growth factor (EGF) signaling in SW480 colon cancer cells. We found that Y27632, a Rho-kinase inhibitor, dose-dependently induced cell proliferation in these cells. The blockade of EGF stimulation utilizing anti-EGF receptor neutralizing antibodies significantly suppressed cell growth, suggesting that EGF stimulation plays an important role in cell proliferation in SW480 cells. We also found that EGF induced Rho-kinase activation. Interestingly, EGF-induced phosphorylation of both Akt and glycogen synthase kinase-3beta (GSK-3beta), but not p44/p42 mitogen-activated protein (MAP) kinase, were dose-dependently enhanced when the cells were pretreated with Y27632 or fasudil, another Rho-kinase inhibitor. Moreover, whereas EGF increased the phosphorylation of retinoblastoma tumor suppressor protein as well as cyclin D1 protein expression level, pretreatment with Y27632 accelerated them. Taken together, our results suggest that Rho-kinase regulates negatively EGF-induced cell proliferation upstream of Akt/GSK-3beta in colon cancer cells.
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PMID:Rho-kinase regulates negatively the epidermal growth factor-stimulated colon cancer cell proliferation. 2012 78

Previous studies have shown that testisin promotes malignant transformation in cancer cells. To define the mechanism of testisin-induced carcinogenesis, we performed yeast two-hybrid analysis and identified maspin, a tumor suppressor protein, as a testisin-interacting molecule. The direct interaction and cytoplasmic co-localization of testisin with maspin was confirmed by immunoprecipitation and confocal analysis, respectively. In cervical cancer cells, maspin modulated cell death and invasion; however, these effects were inhibited by testisin in parallel experiments. Of interest, the doxorubicin resistance was dramatically reduced by testisin knockdown (P=0.016). Moreover, testisin was found to be over-expressed in cervical cancer samples as compared to matched normal cervical tissues. Thus, we postulate that testisin may promote carcinogenesis by inhibiting tumor suppressor activity of maspin.
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PMID:Interaction of testisin with maspin and its impact on invasion and cell death resistance of cervical cancer cells. 2021 23

Carcinogenesis is determined based on both cell proliferation and death rates. Recent studies demonstrate that heat shock proteins (HSPs) regulate apoptosis. HLJ1, a member of the DnaJ-like Hsp40 family, is a newly identified tumor suppressor protein closely related to relapse and survival in non-small cell lung cancer (NSCLC) patients. However, its role in apoptosis is currently unknown. In this study, NSCLC cell lines displaying varying HLJ1 expression levels were subjected to ultraviolet (UV) irradiation, followed by flow cytometry. Interestingly, the percentages of apoptotic cells in the seven cell lines examined were positively correlated with HLJ1 expression. Enforcing expression of HLJ1 in low-HLJ1 expressing highly invasive cells promoted UV-induced apoptosis through enhancing JNK and caspase-3 activation in NSCLC. Additionally, UV irradiation led to reduced levels of HLJ1 predominantly in apoptotic cells. The pan-caspase inhibitor, zVAD-fmk and caspase-3-specific inhibitor, DEVD-fmk, prevented UV-induced degradation of HLJ1 by the late stage of apoptosis. Further experiments revealed a non-typical caspase-3 cleavage site (MEID) at amino acid 125-128 of HLJ1. Our results collectively suggest that HLJ1 is a novel substrate of caspase-3 during the UV-induced apoptotic process.
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PMID:HLJ1 is a novel caspase-3 substrate and its expression enhances UV-induced apoptosis in non-small cell lung carcinoma. 2049 79

During the initial stages of carcinogenesis, transformation events occur in a single cell within an epithelial monolayer. However, it remains unknown what happens at the interface between normal and transformed epithelial cells during this process. In Drosophila, it has been recently shown that normal and transformed cells compete with each other for survival in an epithelial tissue; however the molecular mechanisms whereby "loser cells" undergo apoptosis are not clearly understood. Lgl (lethal giant larvae) is a tumor suppressor protein and plays a crucial role in oncogenesis in flies and mammals. Here we have examined the involvement of Lgl in cell competition and shown that a novel Lgl-binding protein is involved in Lgl-mediated cell competition. Using biochemical immunoprecipitation methods, we first identified Mahjong as a novel binding partner of Lgl in both flies and mammals. In Drosophila, Mahjong is an essential gene, but zygotic mahjong mutants (mahj(-/-)) do not have obvious patterning defects during embryonic or larval development. However, mahj(-/-) cells undergo apoptosis when surrounded by wild-type cells in the wing disc epithelium. Importantly, comparable phenomena also occur in Mahjong-knockdown mammalian cells; Mahjong-knockdown Madin-Darby canine kidney epithelial cells undergo apoptosis, only when surrounded by non-transformed cells. Similarly, apoptosis of lgl(-/-) cells is induced when they are surrounded by wild-type cells in Drosophila wing discs. Phosphorylation of the c-Jun N-terminal kinase (JNK) is increased in mahj(-/-) or lgl(-/-) mutant cells, and expression of Puckered (Puc), an inhibitor of the JNK pathway, suppresses apoptosis of these mutant cells surrounded by wild-type cells, suggesting that the JNK pathway is involved in mahj- or lgl-mediated cell competition. Finally, we have shown that overexpression of Mahj in lgl(-/-) cells strongly suppresses JNK activation and blocks apoptosis of lgl(-/-) cells in the wild-type wing disc epithelium. These data indicate that Mahjong interacts with Lgl biochemically and genetically and that Mahjong and Lgl function in the same pathway to regulate cellular competitiveness. As far as we are aware, this is the first report that cell competition can occur in a mammalian cell culture system.
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PMID:Involvement of Lgl and Mahjong/VprBP in cell competition. 2080 9

Stress protein mortalin (mtHSP70) is highly expressed in cancer cells. It was shown to contribute to carcinogenesis by sequestrating the wild type p53, a key tumor suppressor protein, in the cytoplasm resulting in an abrogation of its transcriptional activation function. We have found that the level of mortalin expression has significant correlation with human hepatocellular carcinoma (HCC) malignancy and therefore investigated whether it interacts with and influences the activities of mutant p53, frequently associated with HCC development. We have detected mortalin-p53 interactions in liver tumor and five HCC cell lines that harbored mutant p53. The data was in contrast to the normal liver and immortalized normal hepatocytes that lacked mortalin-p53 interaction. Furthermore, we have found that the shRNA-mediated mortalin silencing could induce mutant p53-mediated tumor-specific apoptosis in HCC. Such allotment of apoptotic function to mutant p53 by targeting mortalin-p53 interaction in cancer cells is a promising strategy for HCC therapy.
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PMID:Induction of mutant p53-dependent apoptosis in human hepatocellular carcinoma by targeting stress protein mortalin. 2116 51

Schistosoma haematobium is a parasitic flatworm that infects millions of people, mostly in the developing world, and is associated with high incidence of bladder cancer although why is not clear. But our group was able to define the mechanistic relationship for the first time between infection of S. haematobium and cancer. We used in vitro models to demonstrate the presence of informative carcinogenesis-associated phenotypes in CHO cells exposed to Sh total antigen, in which we showed increased cell proliferation, decreased apoptosis, up regulation of the anti-apoptotic molecule Bcl-2, down regulation of the tumor suppressor protein p27, and increased cell migration and invasion. We further discuss the molecular and cellular events that might be responsible for schistosomiasis-related bladder cancer.
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PMID:Schistosoma haematobium and bladder cancer: what lies beneath? 2117 21

Helicobacter pylori (H. pylori) is a gram-negative, spiral-shaped bacterium that infects more than half of the world's population and is a major cause of gastric adenocarcinoma. The mechanisms that link H. pylori infection to gastric carcinogenesis are not well understood. In the present study, we report that the Raf-kinase inhibitor protein (RKIP) has a role in the induction of apoptosis by H. pylori in gastric epithelial cells. Western blot and luciferase transcription reporter assays demonstrate that the pathogenicity island of H. pylori rapidly phosphorylates RKIP, which then localizes to the nucleus where it activates its own transcription and induces apoptosis. Forced overexpression of RKIP enhances apoptosis in H. pylori-infected cells, whereas RKIP RNA inhibition suppresses the induction of apoptosis by H. pylori infection. While inducing the phosphorylation of RKIP, H. pylori simultaneously targets non-phosphorylated RKIP for proteasome-mediated degradation. The increase in RKIP transcription and phosphorylation is abrogated by mutating RKIP serine 153 to valine, demonstrating that regulation of RKIP activity by H. pylori is dependent upon RKIP's S153 residue. In addition, H. pylori infection increases the expression of Snail, a transcriptional repressor of RKIP. Our results suggest that H. pylori utilizes a tumor suppressor protein, RKIP, to promote apoptosis in gastric cancer cells.
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PMID:Regulation of RKIP function by Helicobacter pylori in gastric cancer. 2266 30

Increasing evidence shows the beneficial effects of fish oil on breast cancer growth and invasion in vitro and in animal models. Expression of CSF-1 (colony stimulating factor-1) by breast cancer cells acts as potent activator of malignancy and metastasis. In this report, we used two human breast cancer cell lines, MDA-MB-231 and MCF-7, to show that the bioactive fish oil component DHA (docosahexaenoic acid) inhibits expression of CSF-1 and its secretion from these cancer cells. We found that the tumor suppressor protein PTEN regulates CSF-1 expression through PI 3 kinase/Akt signaling via a transcriptional mechanism. The enhanced abundance of microRNA-21 (miR-21) in breast cancer cells contributes to the growth and metastasis. Interestingly, DHA significantly inhibited expression of miR-21. miR-21 Sponge, which derepresses the miR-21 targets, markedly decreased expression of CSF-1 and its secretion. Furthermore, miR-21-induced upregulation of CSF-1 mRNA and its transcription were prevented by expression of PTEN mRNA lacking 3'-untranslated region (UTR) and miR-21 recognition sequence. Strikingly, miR-21 reversed DHA-forced reduction of CSF-1 expression and secretion. Finally, we found that expression of miR-21 as well as CSF-1 was significantly attenuated in breast tumors of mice receiving a diet supplemented with fish oil. Our results reveal a novel mechanism for the therapeutic function of fish oil diet that blocks miR-21, thereby increasing PTEN levels to prevent expression of CSF-1 in breast cancer.
Carcinogenesis 2012 Oct
PMID:miR-21 is targeted by omega-3 polyunsaturated fatty acid to regulate breast tumor CSF-1 expression. 2267 16


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