UMLS:C1326912 - FACTA Search

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Query: UMLS:C1326912 (tumorigenesis)
57,481 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pentachlorophenol (PCP) is a widely used biocidal compound with several industrial, agricultural and domestic applications. Although it has been shown to induce systemic toxicity and carcinogenesis in several experimental studies, the literature is scarce regarding its toxic mechanisms of action. Recent investigations in our laboratory have shown that PCP induces cytotoxicity and transcriptionally activates stress genes in human liver carcinoma (HepG2) cells [1]. We hypothesized that PCP-induced expression of stress proteins may play a role in the molecular events leading to toxicity and tumorigenesis in liver cells. To test this hypothesis, we performed the MTT-assay for cell viability, and the Western Blot and densitometric analyses to assess the expression of cellular protein including CYP1A1, c-fos, HSP70, and p53. Data obtained from the MTT-assay indicated a strong dose-relationship with respect to PCP cytotoxicity. The LD50 was computed to be 23.0 +/- 5.6 micrograms/mL. Western Blot and densitometric analyses also demonstrated a linear dose-response relationship with regard to CYP1A1 expression within the dose range of 0-50 micrograms/mL. However, a biphasic response was obtained with regard to HSP70, c-fos, and p53 expression, showing a peak induction at 25 micrograms/mL, and a drastic reduction in protein expression at 50 micrograms/mL, probably due to cell death at higher level of PCP exposure. At lower level of exposure, PCP was found to be mitogenic.
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PMID:CYP1a1, HSP70, P53, and c-fos expression in human liver carcinoma cells (HepG2) exposed to pentachlorophenol. 1272 25

Uncontrolled cell proliferation is the basic feature of cancer. Some of the prime cell cycle regulators are involved directly in tumorigenesis. Cyclin A, one of the G(1)/S cyclin, can cause transformation. The purpose of this research was to investigate whether cyclin A overexpression was involved in leukemogenesis and proliferation of leukemia cells. The expression of cyclin A at S-phase in leukemia cell line HL-60, blast cells of acute leukemia patients, bone marrow cells of outpatients without malignant hematological disease and peripheral blood cells of healthy donors was investigated by simultaneous indirect immunofluorescence staining of intracellular antigen and DNA. To further investigate whether cyclin A played as a key molecular in cell proliferation, HL-60 cells were exposed to different concentrations of hexamethylene bisacetamide (HMBA). MTT dye absorbance of living cells and cell cycle analysis were adopted to evaluate growth arrest. Differentiation was evaluated by detection of the change of expression of CD11b and CD33 on cell surface. The results showed that overexpression of cyclin A was only found among specimens from acute leukemia and leukemia cell line. There was no elevated cyclin A detection for cyclin A among specimens from outpatients and healthy donors. In HMBA interference experiment, HMBA was able to induce growth arrest and monocytic macrophage differentiation of HL-60 cells in a dose-dependent manner, and all these changes were associated with a marked down-regulation of cyclin A expression. In conclusion, aberrant overexpression of cyclin A at S-phase was only found in leukemia cell lines and blast cells from acute leukemia. The dose-dependent effect of HMBA on cell growth and differentiation of HL-60 cell line which was consistent with the decrease of cyclin A expression in these cells suggested that the molecular mechanisms of HMBA inducement involved downregulation of cyclin A expression.
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PMID:Clinical and laboratory studies of expression of cyclin A in leukemia cells. 1274 36

Arsenic is a naturally occurring element, but anthropogenic activities can lead to a substantial contamination of the environment. Exposure to arsenic has been associated with a significant number of adverse health effects in humans including: cardiovascular disease, diabetes, hearing loss, developmental abnormalities, anemia, neurologic and neurobehavioral disorder, leukopenia, eosinophilia, fibrosis of the liver and the kidney and various neoplasms. However, the cellular and molecular events associated with arsenic toxicity are poorly understood. Also, the precise mechanisms by which arsenic acts as a carcinogen in humans remain to be elucidated. In the present study, we used human liver carcinoma (HepG2) cells as a model to study the molecular mechanisms of arsenic-induced toxicity and carcinogenesis. We hypothesized that arsenic-induced expression of stress genes and related proteins may play a role in the cellular and molecular events leading to toxicity and tumorigenesis in liver cells. To test this hypothesis, we performed the MTT-assay for cell viability, the CAT-Tox (L) assay for gene induction, and the Western Blot analysis to assess the expression of cellular proteins including c-fos, HMTIIA, HSP70 and p53. Data obtained from the MTT assay indicated a strong dose-response relationship with respect to arsenic trioxide toxicity. Upon 48 hr of exposure, the chemical dose required to cause 50% reduction in cell viability (LD50) was computed to be 8.55 +/- 0.58 microg/ml. The CAT-Tox (L) assay showed statistically significant inductions (p<0.05) of c-fos, HMTIIA, and HSP70. Western blot analysis also demonstrated a dose-response relationship with regard to expression of specific cellular proteins. The p53 protein was expressed in arsenic trioxide-treated cells, however, the densitometric analysis did not show any significant differences (p<0.05) between treated and control cells. The lack of a significant induction of p53 may be due to the potential mitogenic effect of arsenic at low levels of arsenic exposure.
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PMID:Arsenic trioxide-induced transcriptional activation of stress genes and expression of related proteins in human liver carcinoma cells (HepG2). 1468 89

Accumulating evidences indicate that cyclooxygenase (COX)-2 plays an important role in tumorigenesis in many human cancers. Yet the relationship between COX-2 and human renal cell carcinoma (RCC) remains unclear. The aim of our study was to evaluate COX-2 expression in human RCC cell lines and its role in tumorigenesis of human RCC. Among the human RCC cell lines (SMKT-R4, OS-RC-2, ACHN) and normal renal cell line RPTEC, COX-2 overexpression was found in OS-RC-2 cells both at mRNA and protein levels. COX-2 sense- and antisense-orientated vectors were constructed and transferred into RCC cells. Significant suppression of cellular proliferation was demonstrated in OS-RC-2 antisense transfectants, whereas promotion was found in SMKT-R4 sense transfectants by colony-forming assay despite the observation that COX-2 specific inhibitor NS398 exhibited similar IC50 among RCC cell lines by MTT assay. In comparison with parent cells and sense transfectants, significant suppression of COX-2 expression and PGE2 production and increase in butyrate-induced apoptosis were observed in OS-RC-2 antisense transfectants by Western blot, ELISA assay and FACS analysis, respectively. Furthermore, tumor growth and angiogenesis of OS-RC-2 antisense transfectants in nude mice was significantly suppressed and the survival time of these mice was significantly prolonged. Our study demonstrates that COX-2 is overexpressed in OS-RC-2 RCC cell line and plays an important role in tumorigenesis of the cells in vivo, which implies that COX-2 may be a therapeutic target for COX-2-expressing RCC, and that suppression of COX-2 expression by antisense-based strategy may have potential utility in treatment of COX-2-expressing RCC.
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PMID:Significance of COX-2 expression in human renal cell carcinoma cell lines. 1471 83

Cooking oil fumes (COF) exposure was demonstrated to be associated with lung cancer development in Taiwanese nonsmoking women. Previous studies identified Cox-2 overexpression and oxidative DNA damage in lung adenocarcinoma cells after exposure to COF. Involvement of COF in lung tumorigenesis may be associated with cell survival, as well as proliferation of lung adenocarcinoma. To test this hypothesis, A549, a lung adenocarcinoma cell line, was used, and MTT assay data showed that the cell viability of A549 was significantly increased in a concentration-dependent manner by COF treatment for 48 h. Flow cytometery results indicated that the proportion of A549 cell at S-phase was markedly increased after exposure of COF. To elucidate whether the anti-apoptotic c-IAP2 (IAP2) was involved in COF-improved cell survival, IAP2 protein levels was determined by Western blot, and the results showed it was significantly induced by COF in a concentration-dependent manner. Moreover, the suppression of BAY, a nuclear factor (NF)-kappaB binding inhibitor, or the COF-induced IAP2 protein levels indicated that NF-kappaB activation by COF may partly be involved in IAP2 induction. These results showed that the positive impact of COF on cell survival and proliferation of A549 lung tumor cells may be through an induction of IAP2 overexpression.
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PMID:Cooking oil fumes improve lung adenocarcinoma cell survival through c-IAP2 induction. 1607 64

Neural cell adhesion molecule (NCAM) is a type of cell surface glycoprotein and a member of the immunoglobulin superfamily. It has been reported that NCAM may be associated with perineural invasion by malignant salivary gland tumors such as adenoid cystic carcinoma. We have previously demonstrated that NCAM is constitutively expressed in the human salivary gland tumor cell line HSG, in vitro. In the present study, we have aimed to clarify the hypothesis that NCAM-mediated inhibition of salivary gland tumor proliferation is caused by homophilic binding and involves the prevention of signal transduction for perineural invasion using HSG cells. NCAM mRNA and protein expression was found to decrease in a dose-dependent manner upon treatment with the anti-NCAM antibody (MAb NCAM) for 24 h. The MTT assay showed a significant reduction in the number of viable HSG cells. Confocal laser microscopy showed that HSG cells underwent apoptosis after treatment with MAb NCAM. The activation of caspases 3, 7 and 9 was observed in HSG cells after treatment with MAb NCAM, thus confirming that apoptosis was induced by the activated caspases. Apaf-1 activity was also detected in HSG cells in a dose-dependent manner after treatment with MAb NCAM. The up-regulation of TGF-beta1-mediated NCAM expression appeared to lead to the activation of homophilic NCAM binding, further accelerating HSG cell proliferation. In addition, the localization of NCAM in adenoid cystic carcinomas (ACCs) was examined using an immunohistochemical method. NCAM was slightly to moderately positive in 9 of 13 cases (69.2%) of ACC. These findings suggest that NCAM is associated not only with a cell-to-cell adhesion mechanism, but also with tumorigenesis, including growth, development and perineural invasion in human salivary gland tumors.
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PMID:Induction of apoptosis in human salivary gland tumor cells by anti-NCAM antibody. 1621 Dec 77

The aquaporins represent a family of transmembrane water channel proteins that play a major role in trans-cellular and transepithelial water movement. Most tumors have been shown to exhibit high vascular permeability and interstitial fluid pressure, but the transport pathways for water within tumors remain unknown. Here, we tested 10 non-small cell lung cancer cell lines of various origins by reverse transcriptase-polymerase chain reaction and Western blot analysis and identified clear expression of aquaporin 1 (AQP1) in seven cell lines. We next examined the distribution of the AQP1 protein in several types of primary lung tumors (16 squamous cell carcinomas, 21 adenocarcinomas, and 7 bronchoalveolar carcinomas) by immunohistochemical staining. AQP1 was overexpressed in 62% (13 of 21) and 75% (6 of 8) of adenocarcinoma and bronchoalveolar carcinoma, respectively, whereas all cases of squamous cell carcinoma and normal lung tissue were negative. Forced expression of full-length AQP1 cDNA in NIH-3T3 cells induced many phenotypic changes characteristic of transformation, including cell proliferation-enhancing activity by the MTT assay and anchorage-independent growth in soft agar. Although further details on the molecular function of AQP1 related to tumorigenesis remain to be elucidated, our results suggest a potential role of AQP1 as a novel therapeutic target for the management of lung cancer.
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PMID:Aquaporin 1 is overexpressed in lung cancer and stimulates NIH-3T3 cell proliferation and anchorage-independent growth. 2290 56

Telomerase is implicated in the development of cellular immortality and oncogenesis. It has been shown that telomerase activity is considerably higher in the tissue of many different cancers than in normal tissue, and that the inhibition or downregulation of telomerase activity can prevent the malignant proliferation of tumor cells. Antisense oligonucleotides have been widely used in suppressing the expression of genes and, therefore, in the present research, we evaluated the effect of antisense human telomerase RNA (hTR) on glioma cell growth in vitro and in vivo. We showed that antisense hTR cDNA significantly inhibited TJ905 human glioma cell proliferation in vitro and tumor growth in vivo, as determined by MTT assay and by measuring the volume of glioma in nude mice. Consistent with these results, we found that telomerase activity and the mRNA levels of hTR and hTERT (human telomerase reverse transcriptase) expression were markedly decreased in tumor cells treated with antisense hTR cDNA, as assessed by TRAP (telomeric repeat amplification protocol) assay and RT-PCR (reverse transcription-polymerase chain reaction) analysis. Our study conclusively demonstrates that antisense hTR effectively inhibits the growth of human glioma cells in vitro and in vivo and, thus, may be potentially used for gene therapy of malignant gliomas and other cancers.
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PMID:Antisense telomerase RNA inhibits the growth of human glioma cells in vitro and in vivo. 1659 39

Neuregulins are a family of growth factor domain proteins that are structurally related to the epidermal growth factor. Accumulating evidence has shown that neuregulins have cyto- and neuroprotective properties in various cell types. In particular, the neuregulin-1 Beta (NRG1-Beta) isoform is well documented for its antiinflammatory properties in rat brain after acute stroke episodes. Pentachlorophenol (PCP) is an organochlorine compound that has been widely used as a biocide in several industrial, agricultural, and domestic applications. Previous investigations from our laboratory have demonstrated that PCP exerts both cytotoxic and mitogenic effects in human liver carcinoma (HepG2) cells, primary catfish hepatocytes and AML 12 mouse hepatocytes. We have also shown that in HepG2 cells, PCP has the ability to induce stress genes that may play a role in the molecular events leading to toxicity and tumorigenesis. In the present study, we hypothesize that NRG1-Beta will exert its cytoprotective effects in PCP-treated AML 12 mouse hepatocytes by its ability to suppress the toxic effects of PCP. To test this hypothesis, we performed the MTT-cell respiration assay to assess cell viability, and Western-blot analysis to assess stress-related proteins as a consequence of PCP exposure. Data obtained from 48 h-viability studies demonstrated a biphasic response; showing a dose-dependent increase in cell viability within the range of 0 to 3.87 microg/mL, and a gradual decrease within the concentration range of 7.75 to 31.0 microg/mL in concomitant treatments of NRG1-Beta+PCP and PCP. Cell viability percentages indicated that NRG1-Beta+PCPtreated cells were not significantly impaired, while PCP-treated cells were appreciably affected; suggesting that NRG1-Beta has the ability to suppress the toxic effects of PCP. Western Blot analysis demonstrated the potential of PCP to induce oxidative stress and inflammatory response (c-fos), growth arrest and DNA damage (GADD153), proteotoxic effects (HSP70), cell cycle arrest as consequence of DNA damage (p53), mitogenic response (cyclin- D1), and apoptosis (caspase-3). NRG1-Beta exposure attenuated stress-related protein expression in PCP-treated AML 12 mouse hepatocytes. Here we provide clear evidence that NRG1-Beta exerts cytoprotective effects in AML 12 mouse hepatocytes exposed to PCP.
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PMID:Neuregulin 1-Beta cytoprotective role in AML 12 mouse hepatocytes exposed to pentachlorophenol. 1682 72

The purpose of this study was to determine the effect of the FHIT gene on tumorigenesis of cervical cancer. RT-PCR and MTT were used to detect the expression of FHIT and cell proliferation respectively. Flow cytometry was used to test cell cycle and cell apoptosis. The expression of FHIT was not induced at all four cervical cancer cells treated with demethylating agent 5-aza-2'-deoxycytidine (5-Aza-CdR). However, a constant level of FHIT expression was detected in the human umbilical vein endothelial cell before and after 5-aza-dC treatment. The proliferation of all four cervical cancer cells was inhibited evidently when treated with 5-aza-dC and the inhibiting rate of cell growth along with the increasing concentration of 5-aza-dC. There was no obvious inhibiting effect on the growth of the human umbilical vein endothelial cell treated with 5-aza-dC. An increasing G1 phase and high apoptosis rate were detected in all four cervical cancer cells. However, a negligible change was seen in the human umbilical vein endothelial cell. These results suggest that aberrant methylation of the FHIT gene might be a key mechanism for silenced FHIT gene, which could be reactivated and whose tumor suppressing function could be restored by demethylating agent treatment.
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PMID:Regulation of DNA methylation on the expression of the FHIT gene contributes to cervical carcinoma cell tumorigenesis. 1686 65

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