Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ultrastructure of neuroblastoma was examined using unstained sections so that ferritin particles could be identified by the electron density of their iron cores. Ferritin and hemosiderin were found in ten of 11 neuroblastomas that were examined when the patients first presented. The study was therefore expanded to an additional group of children, including some diagnosed by noninvasive procedures and given chemotherapy before the excision of their tumors. In this second group 12 of 20 specimens contained ferritin and hemosiderin in variable amounts. In both groups there was a tendency for patients with advanced disease to have increased amounts of iron compounds in the tumor tissue (Stage III and particularly Stage IV). Most Stage IV patients also had elevated serum ferritin levels. However, based on the available heterogenous material, no absolute relationship could be established between age, disease stage, tumoral storage iron, and the level of serum ferritin. The presence of ferritin in neuroblastoma may be linked to the elevated serum ferritin levels and may be implicated in tumorigenesis.
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PMID:Neuroblastomas contain iron-rich ferritin. 336 71

A trophoblast-like cell line, TL, was established from a normal-term human placenta. The TL cells were epithelial in morphology with relatively large vesicular nuclei, prominent nucleoli, and numerous microvilli on the cell surface. Cytoplasmic organelles were generally sparse but mitochondria and polysomes were abundant. The cells grew as compact sheets with close membrane approximation interconnected occasionally by desmosome-like junctions. TL cells contained placental alkaline phosphatase, a placenta-associated antigen, cytokeratin, and prekeratin, but not keratin. In parallel, they were negative for factor VIII, vimentin, and fibronectin. Population doubling time was estimated to be about 34 h. TL cells were tumorigenic in nude mice and an increase in tumorigenicity was observed after a certain number of passages in vitro. Chromosome analysis revealed that TL cells were highly heterogenous and had a female aneuploid karyotype with a hypotriploid mode. Unlike trophoblastic cell lines established from neoplastic tissues, TL cells did not synthesize human chorionic gonadotropin or other gonadal hormones, and only a small amount of ferritin (40.3 ng/10(6) cells) could be detected in the cell supernatant and cell extract. Based on various morphological and histochemical criteria, we suggest that the TL cells are derived from the Langhans cells (villous cytotrophoblast), and due to their special features, the cells may be valuable for the study of the differentiation and tumorigenesis of trophoblastic cells.
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PMID:Establishment and characterization of a tumorigenic trophoblast-like cell line from a human placenta. 358 Oct 66

Many studies indicate that animals and humans burdened with excess iron are at increased risk of neoplasia at various sites. This review focuses on inquiries that involve iron and colorectal cancer. Relevant studies reported in the past decade are briefly described and evaluated. The studies in animal models and in relatively large groups of humans point to a positive association of excessive iron with colorectal oncogenesis. Phytic acid, a chelator of iron and zinc, may be useful in withholding iron from the carcinogenic process. Sufficient evidence is available to justify construction of long-term prospective studies in humans in which would be monitored (i) levels of iron and phytate intake, (ii) serum transferrin iron saturation and ferritin, (iii) fecal levels of iron and hydroxyl radicals, and (iv) appearance of colorectal polyps, adenomas and carcinomas.
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PMID:Association of iron with colorectal cancer. 804 85

Dithiolethiones inhibit tumorigenicity elicited by many structurally diverse carcinogens in numerous target tissues. These protective actions are associated with the induction of several carcinogen detoxification enzymes, some of which have only recently been discovered. In order to identify additional novel inducible detoxification response genes, a cDNA library was prepared from liver of rats treated with 1,2-dithiole-3-thione (D3T) and was screened by a differential hybridization method. Complementary DNA clones for several known D3T-inducible genes were isolated, such as epoxide hydrolase, aflatoxin B1-aldehyde reductase, quinone reductase and multiple subunits of glutathione S-transferase. Clones representing genes not previously associated with detoxification were isolated, including those for ferritin heavy and light subunits, ribosomal proteins L18a and S16 and two novel genes, termed dithiolethione-inducible genes (or DIG-1 and DIG-2). Levels of mRNA recognized by each clone were increased from 2- to 31-fold, with maximum induction between 6 and 30 h after treatment with D3T. Except for epoxide hydrolase, the kinetics of induction of each mRNA was coordinate with increased rates of gene transcription. However, based on the time of response to D3T, at least two sets of responsive genes were identified. One set of genes, including glutathione S-transferase Yp, aflatoxin B1-aldehyde reductase, quinone reductase and DIG-1, had low constitutive and highly inducible expression (approximately 20-fold) and the other, including glutathione S-transferase Ya and Yb, epoxide hydrolase, ferritin heavy and light subunits, ribosomal proteins L18a and S16 and DIG-2, had relatively high constitutive and modestly inducible expression (approximately 5-fold). The simplest explanation for this differential expression of D3T-inducible genes is that multiple regulatory mechanisms govern their response. The transcriptional activation of ferritin, ribosomal protein, DIG-1 and DIG-2 genes in conjunction with those of carcinogen detoxification enzymes suggests that they participate in the pleiotropic cellular defense response to dithiolethiones that inhibits chemically produced tumorigenesis.
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PMID:Isolation of cDNAs representing dithiolethione-responsive genes. 896 41

A family of non-coding sequences in the mRNA (iso-IREs [iron-responsive elements]) regulate synthesis of key proteins in animal iron and oxidative metabolism such as ferritin and mitochondrial aconitase. Differential recognition between iso-IREs and iso-IRPs (iron regulatory proteins) regulates the translation or degradation of the IRE-containing mRNAs. IREs are hairpin loop structures with an internal loop/bulge or bulge that influence the binding of the iso-IRPs. The iso-IRPs have sequence homology to the aconitases and at least one IRP can be converted to an aconitase. Signals that target the iso-IRE/iso-IRP interactions in mRNA include environmental iron, O2, nitric oxide, H2O2, ascorbate, growth factors, and protein kinase C-dependent IRP phosphorylation. Iso-IRE structural specificity suggests a means of pharmacologically targeting mRNA function with chemicals such as Fe-bleomycin and other transition metal complexes that could be extended to other mRNAs with specific structures. With the iso-IRE/iso-IRP system, nature has evolved coordinated combinatorial control of iron and oxygen metabolism that may exemplify control of mRNAs in other metabolic pathways, viral reproduction, and oncogenesis.
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PMID:Targeting mRNA to regulate iron and oxygen metabolism. 1060 37

NF-kappaB/Rel transcription factors block apoptosis or programmed cell death (PCD) induced by tumor necrosis factor (TNF) alpha. The antiapoptotic activity of NF-kappaB is also crucial for immunity, lymphocyte development, tumorigenesis, and cancer chemoresistance. With respect to TNFalpha, the NF-kappaB-mediated suppression of apoptosis involves inhibition of the c-Jun-N-terminal kinase (JNK) cascade. This inhibitory activity of NF-kappaB depends upon transcriptional upregulation of blockers of the JNK cascade such as the caspase inhibitor XIAP, the zinc-finger protein A20, and the inhibitor of the MKK7/JNKK2 kinase Gadd45beta/Myd118. Moreover, NF-kappaB blunts accumulation of reactive oxygen species (ROS) induced by TNFalpha, and this antioxidant effect of NF-kappaB is also critical for inhibition of TNFalpha-induced JNK activation. Suppression of ROS by NF-kappaB is mediated by Ferritin heavy chain (FHC)--the primary iron-storage mechanism in cells--and possibly, by the mitochondrial enzyme Mn++ superoxide dismutase (Mn-SOD). Thus, induction of FHC and Mn-SOD represents an additional, indirect means by which NF-kappaB controls proapoptotic JNK signaling. These findings identify potential new targets for anti-inflammatory and anti-cancer therapy.
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PMID:NF-kappaB and JNK: an intricate affair. 1561 22

NF-kappaB/Rel transcription factors are best known for their roles in innate and adaptive immunity and inflammation. They also play a central role in promoting cell survival. This latter activity of NF-kappaB antagonizes programmed cell death (PCD) induced by the proinflammatory cytokine tumor necrosis factor (TNF)alpha and plays an important role in immunity, lymphopoiesis, osteogenesis, tumorigenesis and radio- and chemoresistance in cancer. With regard to TNFalpha, the NF-kappaB-mediated inhibition of PCD seems to involve an attenuation of the c-Jun-N-terminal kinase (JNK) cascade mediated through the induction of select downstream targets such as the caspase inhibitor XIAP, the zinc-finger protein A20, and the inhibitor of the MKK7/JNKK2 kinase, Gadd45beta/Myd118. Notably, NF-kappaB also blunts accumulation of reactive oxygen species (ROS), which themselves are pivotal elements for induction of PCD by TNFalpha, and this suppression of ROS formation mediates an additional protective activity recently ascribed to NF-kappaB. The antioxidant activity of NF-kappaB has been shown to depend upon upregulation of both Ferritin heavy chain (FHC)--a component of Ferritin, the primary iron-storage protein complex found in cells--and of the mitochondrial enzyme Mn++ superoxide dismutase (Mn-SOD). Indeed, the inductions of Mn-SOD and FHC represent another important means through which NF-kappaB controls proapoptotic JNK signaling triggered by TNFalpha. These findings might enable the development of new, more targeted approaches to treatment of diseases sustained by a deregulated activity of NF-kappaB, including some cancers and chronic inflammatory conditions.
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PMID:The NF-kappaB-mediated control of ROS and JNK signaling. 1626 88

H-ferritin (HF) is a core subunit of the iron storage protein ferritin and is related to the pathogenesis of malignant diseases. HF overexpression is present in human hematologic malignancies, suggesting that HF overexpression may contribute to the development of hematologic cancers. However, in vivo evidence that HF is directly linked to hematologic tumorigenesis has not yet been shown. In this study, we show that transgenic (tg) mice overexpressing the human HF gene (hHF-tg) developed aggressive radiation-induced thymic lymphoma/leukemia (TL) compared with wild-type (WT) mice, providing evidence that HF overexpression promotes leukemia/lymphomagenesis. Fractionated X-irradiation of hHF-tg mice caused a higher incidence and earlier onset of TL compared with WT mice. Immunological and pathological features of TLs were similar in both groups. However, proliferative activity of hHF-tg lymphoma cells was higher than that of WT lymphoma cells, and microarray analyses revealed that some leukemia/lymphoma-related genes were differentially expressed in hHF-tg TLs compared with WT TLs. To investigate whether cell damage induced by irradiation is related to leukemia/lymphomagenesis, we evaluated apoptotic levels in the thymus and bone marrow (BM) of hHF-tg and WT groups after fractionated X-irradiation. Apoptosis was augmented in the hHF-tg BM, but not in the thymus, compared with the WT BM, suggesting a possible linkage between increased BM apoptosis by HF overexpression and accelerated radiation-induced TL development. Our findings indicate that HF overexpression is closely related to the development of leukemia/lymphoma, which could have implications for the prevention of malignant hematologic diseases.
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PMID:H-ferritin overexpression promotes radiation-induced leukemia/lymphoma in mice. 2284 5

Human epidermal growth factor receptor 2 (HER2) overexpression leads to mammary tumorigenesis and its elevated levels lead to increase in cancer stem cells (CSCs), invasion, and metastasis. CSCs are resistant to radiation/chemotherapeutic drugs and are believed to be responsible for recurrence/relapse of cancer. CSCs are isolated using flow cytometry based sorting, although reliable, this technology hinders the convenient identification of molecular targets of CSCs. Therefore to understand the molecular players of increased CSC through HER2 overexpression and to develop meaningful targets for combination therapy, we isolated and characterized breast CSCs through convenient tumorsphere culture. We identified the altered protein expression in CSC as compared to non-CSC using LC-MS/MS and confirmed those results using qRT-PCR and Western blotting. Ferritin heavy chain 1 (FTH1) was identified as a candidate gene, which is involved in iron metabolism and iron depletion significantly decreased the self-renewal of CSCs. We further performed in silico analysis of altered genes in tumorsphere and identified a set of genes (PTMA, S100A4, S100A6, TNXRD1, COX-1, COX-2, KRT14, and FTH1), representing possible molecular targets, which in combination showed a promise to be used as prognostic markers for breast cancer.
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PMID:Proteomic profiling of cancer stem cells derived from primary tumors of HER2/Neu transgenic mice. 2299 41

Tumor-associated macrophages play a critical role in breast tumor progression; however, it is still unclear what effector molecular mechanisms they employ to impact tumorigenesis. Ferritin is the primary intracellular iron storage protein and is also abundant in circulation. In breast cancer patients, ferritin is detected at higher levels in both serum and tumor lysates, and its increase correlates with poor clinical outcome. In this study, we comprehensively examined the distribution of ferritin in normal and malignant breast tissue at different stages in tumor development. Decreased ferritin expression in cancer cells but increased infiltration of ferritin-rich CD68-positive macrophages was observed with increased tumor histological grade. Interestingly, ferritin stained within the stroma surrounding tumors suggesting local release within the breast. In cell culture, macrophages, but not breast cancer cells, were capable of ferritin secretion, and this secretion was further increased in response to pro-inflammatory cytokines. We next examined the possible functional significance of extracellular ferritin in a breast cancer cell culture model. Ferritin stimulated the proliferation of the epithelial breast cancer cell lines MCF7 and T47D. Moreover, this proliferative effect was independent of the iron content of ferritin and did not increase intracellular iron levels in cancer cells indicating a novel iron-independent function for this protein. Together, these findings suggest that the release of ferritin by infiltrating macrophages in breast tumors may represent an inflammatory effector mechanism by which ferritin directly stimulates tumorigenesis.
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PMID:Ferritin stimulates breast cancer cells through an iron-independent mechanism and is localized within tumor-associated macrophages. 2330 63


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