Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001418 (adenocarcinoma)
 68,496 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the human prostate, a low affinity (p75) nerve growth factor (NGF) receptor (NGF-R) localizes to the epithelia while a NGF-like protein localizes to the stroma. This NGF-like ligand, derived from prostate stromal cell cultures, has been shown to participate in paracrine mediated growth of a human tumor epithelial cell line (TSU-prl) in vitro. In order to investigate the role of the NGF-R in neoplastic growth we have examined the expression of the NGF-R in normal prostate tissues, benign prostatic hyperplasia tissues, adenocarcinoma tissues, and four metastatic tumor cell lines of the human prostate. In primary epithelial cell cultures of normal human prostate the p75 NGF-R was localized by immunocytochemistry to cytoplasmic vesicles. Furthermore, Western blot analysis of the NGF-R in subcellular fractions of normal prostate tissue identified an M(r) 75,000 immunoreactive protein in the microsomal fraction under nonreducing conditions of sodium dodecyl sulfatepolyacrylamide gel electrophoresis. However, microsomal preparations of five prostatic adenocarcinoma and five benign prostatic hyperplasia specimens showed varying immunoreactivity among samples, all of which expressed less of the p75 NGF-R than the normal tissue. Interestingly, microsomal preparations of the human prostatic epithelial cell lines, TSU-prl, DU-145, PC-3, and LNCaP did not show NGF-R expression by immunoblot analysis. Hence, expression of the p75 NGF-R in normal prostate tissue, partial loss of NGF-R expression in benign and malignant prostate tissue, and complete loss of NGF-R expression in the four metastatic tumor cell lines, suggests an inverse association of p75 NGF-R expression with the neoplastic progression of the human prostate.
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PMID:Reduced expression of the low affinity nerve growth factor receptor in benign and malignant human prostate tissue and loss of expression in four human metastatic prostate tumor cell lines. 138 43

In order to examine the effects of the overexpression of c-erbB-2 (HER-2, neu) on human bronchial epithelial cells, a human c-erbB-2 expression vector was introduced into the simian virus 40 large T-antigen-immortalized human bronchial epithelial cell line BEAS-2B. Isolation of multiple clonal cell lines after selection revealed a wide range of expression of the gene product gp185erbB-2. While three of six clones tested expressed gp185erbB-2 at levels detectable by immunocytochemistry, only one, B2BE6, induced adenocarcinoma-like tumors in athymic nude mice. Both a nontumorigenic clone, B2BE2, and a tumorigenic clone, B2BE6, expressed comparable amounts of gp185erbB-2, which became phosphorylated on tyrosine in response to treatment with the c-erbB-2 ligands gp30 and p75. These data suggest that overexpression of c-erbB-2 in human bronchial epithelial cells can contribute to, but is not sufficient for, induction of tumorigenicity in this human model system.
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PMID:Biological consequences of overexpression of a transfected c-erbB-2 gene in immortalized human bronchial epithelial cells. 768 50

The molecular basis of cross-resistance to tumor necrosis factor (TNF) and Adriamycin has been investigated using the breast adenocarcinoma cell line MCF7/p, its Adriamycin-resistant counterpart MCF7AdrR, and the MDR1 gene-transduced MCF-7 cells (MCF7/MDR1). While the parental cell line MCF7/p was TNF-sensitive, MCF7AdrR was TNF-resistant. The TNF resistance exhibited by MCF7AdrR cells was not due to a lack of TNF receptor expression because both cell lines express comparable levels of p75 and p55 receptors as revealed by immunofluorescence analysis. NF-kappa B translocation, which is an essential transducing signal of the TNF-induced lysis pathway, does not appear to be involved in this resistance as assessed by gel shift experiments. In order to determine the role of MDR1 gene expression in the development of this cross-resistance, MCF7/p cells transfected by the MDR1 gene were examined. Our data showed that the expression of the MDR1 gene in these cells resulted in a relative resistance of these cells to Adriamycin without affecting their susceptibility to TNF killing. The implication of the manganese superoxide dismutase and endogenous TNF expression in the cross-resistance by MCF7AdrR cells to Adriamycin and TNF has also been investigated. Northern blot analysis indicated that following TNF stimulation, the expression of 4-kilobase and 1-kilobase manganese superoxide dismutase mRNAs were 9- to 10-fold induced in MCF7AdrR cells as compared to MCF7/p and MCF7/MDR1 cells. This suggests a possible involvement of this enzyme in the Adriamycin-induced resistance to TNF. Although TNF-treatment of MCF7/p and MDR-cells induced endogenous TNF expression in these cells, the level of mRNA induction was selectively enhanced in MCF7AdrR cells (7- to 8-fold greater in MCF7AdrR cells as compared to MCF7/p and MCF7/MDR1 cells). Collectively, these data indicate that the expression of the MDR1 gene in MCF7/p cells following gene transfection is not sufficient for the acquisition of TNF resistance by MCF7/MDR1 cells. Furthermore, our data provide the first evidence that Adriamycin-induced resistance to TNF in MCF7AdrR cells may, in part, involve an overexpression of endogenous TNF and manganese superoxide dismutase genes.
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PMID:Resistance to TNF-alpha and adriamycin in the human breast cancer MCF-7 cell line: relationship to MDR1, MnSOD, and TNF gene expression. 790 87

The functional role of human tumor necrosis factor receptor (TNFR) p75 was studied by the use of TNFR p75-specific agonistic antibodies. Human SW480T adenocarcinoma cells, stably transfected with a reporter construct containing beta-galactosidase under the control of human cytomegalovirus immediate early enhancer, were stimulated with anti-TNFR p75 polyclonal antiserum or monoclonal antibodies followed by measurement of beta-galactosidase activity and analysis by electrophoretic mobility shift assays. It was found that cross-linking of TNFR p75 led to strong induction of the human cytomegalovirus enhancer as well as activation of nuclear factor-kappa B (NF-kappa B). Stimulation of TNFR p75 also mediated activation of NF-kappa B in human KYM-1 rhabdomyosarcoma cells but not in other cell types such as U937 and HL-60 monocytic cells or in Eahy 926 endothelial cells. NF-kappa B activation induced by TNFR p75 was delayed approximately 15 min compared with NF-kappa B activation induced by TNFR p55, indicating that the two TNFRs activate NF-kappa B through different signaling pathways. The data presented in this study identify intracellular responses mediated by TNFR p75 which have not been reported previously and suggest that TNFR p75-induced activation of NF-kappa B is strictly cell type-specific.
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PMID:Tumor necrosis factor receptor p75 mediates cell-specific activation of nuclear factor kappa B and induction of human cytomegalovirus enhancer. 812 5

Tumor necrosis factor (TNF) receptor (TNFR)-associated factors 1 and 2 (TRAF1 and TRAF2) and inhibitor of apoptosis proteins cIAP1 (MIHB) and cIAP2 (MIHC) were recently identified as proteins that associate with the TNF-alpha receptors TNFRI (p55) and TNFRII (p75) and inhibit TNF-alpha-induced programmed cell death or apoptosis. In the original reports, TRAF1 expression, unlike the ubiquitous TRAF2, was restricted to specific tissues in the lung, spleen, and testis. TNF-alpha is increased in the lung in many forms of pulmonary disease. In the current study, Western analysis, immunohistochemistry, and ribonuclease protection assays were used to determine whether TNF-alpha regulates the expression of these TNFR-associated proteins in lung cells. We demonstrate for the first time TNF-alpha dose-dependent induction of TRAF1 protein and messenger RNA (mRNA) in human H441 and A549 pulmonary adenocarcinoma cell lines, as well as in lung cells of C57BL/6J mice after intratracheal administration of TNF-alpha. In contrast to the epithelial cells, TRAF1 was not induced by TNF-alpha in U937 cells, a human monocytic cell line, suggesting cell type-specific regulation. Similarly, cIAP2 mRNA was induced by TNF-alpha in both H441 and A549 pulmonary epithelial cells but not in U937 cells. TNF-alpha is a primary mediator of acute pulmonary inflammation and contributes to the pathophysiology of chronic lung diseases such as bronchopulmonary dysplasia (BPD), a fibrotic disease of prematurely born infants. Immunohistochemical staining of human neonatal lung tissue demonstrated increased TRAF1 in lungs of infants dying of pneumonia or BPD in comparison with those dying of congenital malformation. These studies support the hypothesis that the TRAF1 and cIAP2 genes are highly regulated in pulmonary cells and may play a role in human lung disease.
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PMID:Tumor necrosis factor-alpha-induced lung cell expression of antiapoptotic genes TRAF1 and cIAP2. 1065 35

Although debates still exist whether Helicobacter pylori infection is really class I carcinogen or not, H. pylori has been known to provoke precancerous lesions like gastric adenoma and chronic atrophic gastritis with intestinal metaplasia as well as gastric cancer. Chronic persistent, uncontrolled gastric inflammations are possible basis for ensuing gastric carcinogenesis and H. pylori infection increased COX-2 expressions, which might be the one of the mechanisms leading to gastric cancer. To know the implication of long-term treatment of antiinflammatory drugs, rebamipide or nimesulide, on H. pylori-associated gastric carcinogenesis, we infected C57BL/6 mice with H. pylori, especially after MNU administration to promote carcinogenesis and the effects of the long-term administration of rebamipide or nimesulide were evaluated. C57BL/6 mice were sacrificed 50 weeks after H. pylori infection. Colonization rates of H. pylori, degree of gastric inflammation and other pathological changes including atrophic gastritis and metaplasia, serum levels and mRNA transcripts of various mouse cytokines and chemokines, and NF-kappaB binding activities, and finally the presence of gastric adenocarcinoma were compared between H. pylori infected group (HP), and H. pylori infected group administered with long-term rebamipide containing pellet diets (HPR) or nimesulide mixed pellets (HPN). Gastric mucosal expressions of ICAM-1, HCAM, MMP, and transcriptional regulations of NF-kappaB binding were all significantly decreased in HPR group than in HP group. Multi-probe RNase protection assay showed the significantly decreased mRNA levels of apoptosis related genes and various cytokines genes like IFN-gamma, RANTES, TNF-alpha, TNFR p75, IL-1beta in HPR group. In the experiment designed to provoke gastric cancer through MNU treatment with H. pylori infection, the incidence of gastric carcinoma was not changed between HP and HPR group, but significantly decreased in HPN group, suggesting the chemoprevention of H. pylori-associated gastric carcinogenesis by COX-2 inhibition. Long-term administration of antiinflammatory drugs should be considered in the treatment of H. pylori since they showed the molecular and biologic advantages with possible chemopreventive effect against H. pylori-associated gastric carcinogenesis. If the final concrete proof showing the causal relationship between H. pylori infection and gastric carcinogenesis could be obtained, that will shed new light on chemoprevention of gastric cancer, that is, that gastric cancer could be prevented through either the eradication of H. pylori or lessening the inflammation provoked by H. pylori infection in high risk group.
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PMID:Chemoprevention of Helicobacter pylori-associated gastric carcinogenesis in a mouse model: is it possible? 1254 79

The neurotrophin family of growth factors and their receptors support the survival of several neuronal and non-neuronal cell populations during embryonic development and adult life. Neurotrophins are also involved in malignant transformation. To seek the role of neurotrophin signaling in human lung cancer we studied the expression of neurotrophin receptors in human lung adenocarcinomas and investigated the effect of the neurotrophin receptor inhibitor K252a in A549 cell survival and colony formation ability in soft agar. We showed that human lung adenocarcinomas express TrkA and TrkB, but not TrkC; A549 cells, derived from a human lung adenocarcinoma, express mRNA transcripts encoding nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), TrkA, TrkB, and p75, and high protein levels of TrkA and TrkB. Stimulation of cells using NGF or BDNF activates the anti-apoptotic protein Akt. Interestingly, inhibition of neurotrophin receptor signaling using K252a prevents Akt activation in response to NGF or BDNF, induces apoptotic cell death, and diminishes the ability of A549 cells to growth in soft agar. The data suggest that neurotrophin signaling inhibition using k252a may be a valid therapy to treat patients with lung adenocarcinomas.
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PMID:The Trk tyrosine kinase inhibitor K252a regulates growth of lung adenocarcinomas. 1686 49

Expression of certain neurotrophin genes and their receptors, as well as NGF-induced gene EGRI was studied in human normal lung, squamous cell lung cancer, and adenocarcinoma tissues. Differential expression pattern of NGF, BDNF, and NT-3 mRNA was established by RT-PCR in normal human lung. NGF expression level varying from minor to significant was demonstrated in double specimens (histologically diagnosed human lung cancer and appropriate adjacent tissue). Interestingly, a half of the double specimens studied demonstrated the differential expression pattern in both cancer and adjacent tissues, whereas in other cases no difference in the NGF expression between these pair of tissues was observed. In the majority of the double specimens, we detected low levels of NT3 and BDNF expression for both cancer and adjacent tissue. No expression of TrkA, TrkB, p75 was found in double specimens and normal tissues. Differential expression patterns of TrkC were observed in normal tissues as well as in certain double specimens. High levels of EGR1 expression were detected in normal tissues. No EGRI expression was observed in cancer tissue compared to its high expression level in adjacent tissue in the majority of double specimens.
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PMID:[Expression peculiarities of EGR1, neurotrophins and their receptor genes in human lung cancer and in normal lung tissue]. 1760 Sep 21

The prostate is one of the most abundant sources of nerve growth factor (NGF) in different species, including humans. NGF and its receptors are implicated in the control of prostate cell proliferation and apoptosis and it can either support or suppress cell growth. The co-expression of both NGF receptors, p75(NGFR) and tropomyosin-related kinase A (trkA), represents a crucial condition for the antiproliferative effect of NGF; indeed, p75(NGFR) is progressively lost during prostate tumorigenesis and its disappearance represents a malignancy marker of prostate adenocarcinoma (PCa). Interestingly, a dysregulation of NGF signal transduction was found in a number of human tumors. This review summarizes the current knowledge on the role of NGF and its receptors in prostate and in PCa. Conclusions bring to the hypothesis that the NGF network could be a candidate for future pharmacological manipulation in the PCa therapy: in particular the re-expression of p75(NTR) and/or the negative modulation of trkA could represent a target to induce apoptosis and to reduce proliferation and invasiveness of PCa.
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PMID:Nerve growth factor signaling in prostate health and disease. 2016 99

Lymphocytic infiltrates of the mouse mammary preneoplastic, hyperplastic alveolar nodule (HAN) line C4 have elevated reactivity which correlates positively with the progression of HAN to mammary adenocarcinoma. In this study we investigated the hypothesis that the immunoregulatory mechanisms of HAN infiltrating lymphocytes (HILs) on mammary neoplastic progression are mediated, at least in part, by tumor necrosis factor alpha (TNF alpha). C4 HAN epithelial cells express mRNA for both the p55-60 receptor and the p75-80 TNF alpha receptors. High levels of both TNF alpha and TNF beta are expressed by HILs, whereas only TNF alpha is expressed by the C4 HAN epithelial cells. Treatment of C4 HAN bearers with TNF alpha in vivo decreases the latency period and enhances the frequency of HAN progression to tumor. Proliferation of monolayer cultures of epithelial cells from mammary glands of normal and C4 HAN-bearing mice, as well as C4 tumor cells, is enhanced by TNF alpha. Growth of normal mammary cells in 3-dimensional collagen cultures is also significantly stimulated by TNF alpha. Our results suggest that stimulation of epithelial cell proliferation by HIL-produced TNF alpha is one mechanism responsible for the 'immune stimulation' of neoplastic progression in the HAN model.
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PMID:Tumor necrosis factor alpha-induced stimulation of neoplastic progression of preneoplastic, hyperplastic alveolar nodule line C4. 2153 6


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