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)

Placental isoferritin (PLF), an acidic isoform of ferritin, and its unique superheavy chain p43 have been recently described to be synthesized by breast cancer cell lines but not by normal breast epithelial cells. Since previous reports have demonstrated a correlation between the content of 'normal' ferritin in breast cancer tissue, degree of differentiation, and prognosis, we have tried to evaluate the correlation of p43 in the cytosol of 122 breast cancer samples with commonly applied prognostic factors and features of proliferation and differentiation. In parallel, we investigated the correlation of p43 expression in MCF-7 and T47-D breast cancer cell lines during proliferation induced by estradiol plus fetal calf serum (assessed by 3H-thymidine incorporation), compared to p43 expression in stationary non-stimulated cell cultures. The levels of p43 in breast cancer cytosols correlated significantly negatively with tumor size (p = 0.0001), histologic grading (p = 0.0038), nuclear pleomorphism (p = 0.0019), rate of mitosis (p = 0.0002), and lymphocytic reaction (p = 0.0001), and significantly directly with the estrogen receptor status (p = 0.0009). Although patients with a higher p43 content showed a trend for a better outcome (median follow-up: 61.4 months), an independent influence of the cytosolic p43 content on survival could not be confirmed by a multivariate Cox model. In accordance with the observed negative correlation of features of differentiation vs. p43 expression, induction of proliferation by estradiol plus FCS added to serum-free tissue culture medium correlated with a decrease of p43 synthesis in both cell lines. Expression of p43 in estrogen and FCS-absent media revealed also a decrease in relation to a low spontaneous proliferation. However, the drop of p43 synthesis was significantly stronger in cell lines with estrogen-stimulated proliferation. Our in vitro and cytosol results confirm recent clinical observations describing an inverse correlation of p43 synthesis with the degree of proliferation and differentiation in breast cancer. However, the pathologic mechanisms leading to this phenomenon as well as the negative correlation with lymphocytic infiltration are still unclear and need to be further elucidated.
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PMID:Placental isoferritin associated p43 antigen correlates with features of high differentiation in breast cancer. 146 68

Immunohistological studies on frozen sections of human placentae and breast carcinoma tissue using heteroantisera raised against both trophoblast microvillous plasma membrane preparations isolated from normal placentae and irradiated MCF-7 breast carcinoma cells have demonstrated a cell membrane antigen expressed by both normal human trophoblast and human breast carcinoma cells. The heteroantisera used in this study had all been previously adsorbed with immobilized human term pregnancy serum, placental alkaline phosphatase and placental ferritin preparations, as well as with human peripheral blood leucocytes. The oncoplacental membrane antigen would appear not to be represented in other normal tissues, but is represented on Jar choriocarcinoma cells and to a lesser degree on AV3 amniotic cells. Adsorption experiments have demonstrated that this antigen may not be dominant within the range of antigenic specificities of heteroantisera raised against MCF-7 cells or isolated trophoblast microvillous plasma membrane preparations.
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PMID:A cell membrane antigen expressed by both human breast carcinoma cells and normal human trophoblast. 616 65

Subtractive hybridization was used to isolate genes expressed uniquely in the immortalized human breast epithelial cell (HBEC) line MCF-10F and not in the mortal HBEC line S-130, from which MCF-10F cells were derived. We identified a 233-bp cDNA that was expressed in MCF-10F cells and not in their mortal counterpart S-130 cells. Sequence comparison with the GenBank database revealed that the cDNA was identical to the gene encoding human ferritin heavy H chain. Northern blot analysis using the isolated cDNA as a probe showed a differentially expressed 1.1-kb transcript of ferritin H in total RNA from the immortal MCF-10F cells, MCF-10F cells treated with the chemical carcinogens 7,12-dimethylbenz[a]anthracene and benzo[a]pyrene, and the breast cancer cell lines MCF-7, HBL-100, T-47D, and BT-20. No ferritin H transcript was detected in the mortal line S-130 or in other primary HBEC cultures. Increased levels of mRNA transcript signals were also detected in total RNA from breast cancer tissue samples. Tissue with ductal hyperplasia had higher expression levels than normal adjacent mammary tissue. In situ hybridization showed high levels of ferritin H transcript in mammary tissue areas with ductal hyperplasia, carcinoma in situ, and infiltrating ductal carcinoma. This is the first report of the differential expression and upregulation of human ferritin H chain gene in immortal HBECs. It may be an important factor in the process of immortalization, possibly an early stage of malignant transformation of HBECs, providing cells with iron necessary for growth and clonal expansion. Also, ferritin iron, once released, may increase the level of reactive iron, leading to an increase in oxygen free-radical generation, oxidative DNA damage, and mutation.
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PMID:Differential expression of human ferritin H chain gene in immortal human breast epithelial MCF-10F cells. 943 77

We have elucidated a biochemical mechanism whereby changes in iron metabolism cause changes in folate-dependent one-carbon metabolism. Although animal and clinical studies have demonstrated that perturbations in iron status and metabolism alter folate metabolism, the biochemical mechanisms underlying these associations have yet to be identified. The effect of altered ferritin expression on folate metabolism was determined in human MCF-7 cells and SH-SY5Y neuroblastoma. Cells expressing rat heavy chain ferritin (HCF) exhibited markedly increased expression of the folate-dependent enzyme cytoplasmic serine hydroxymethyltransferase (cSHMT). These effects were not seen when rat light chain ferritin was expressed. Additionally, cSHMT expression was not altered when HCF expression was induced in MCF-7 cells cultured with supplemental ferric citrate. This indicates that cSHMT expression is increased by elevated HCF concentrations, independent of increased iron availability, suggesting that cSHMT expression may respond to HCF-induced chelation of the regulatory iron pool. Increased HCF expression did not alter cSHMT mRNA levels, but did increase translation rates of cSHMT mRNA. The increase in translation was mediated, at least in part, through the cSHMT 5'-untranslated region of the transcript. MCF-7 cells with increased expression of cSHMT displayed increased efficiency of de novo thymidylate biosynthesis, indicating that thymidylate synthesis is normally limited by cSHMT activity in MCF-7 cells. Our data suggest that the iron regulatory pool may play an important role in regulating folate metabolism and thereby thymidine biosynthesis.
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PMID:Heavy chain ferritin enhances serine hydroxymethyltransferase expression and de novo thymidine biosynthesis. 1127 96

Ferritin is a ubiquitous iron storage protein existing in multiple isoforms composed of 24 heavy and light chain subunits. We describe here a third ferritin-related subunit cloned from human placenta cDNA library and named PLIF (placental immunomodulatory ferritin). The PLIF coding region is composed of ferritin heavy chain (FTH) sequence lacking the 65 C-terminal amino acids, which are substituted with a novel 48 amino acid domain (C48). In contrast to FTH, PLIF mRNA does not include the iron response element in the 5'-untranslated region, suggesting that PLIF synthesis is not regulated by iron. The linkage between the FTH and C48 domains created a restriction site for EcoRI. PLIF protein was found to localize in syncytiotrophoblasts of placentas (8 weeks of gestation) at the fetal-maternal interface. Increased levels of PLIF transcript and protein were also detected in the breast carcinoma cell lines T47D and MCF-7 but not in the benign corresponding cell line HBL-100. In vitro, PLIF was shown to down-modulate mixed lymphocyte reactions and to inhibit the proliferation of peripheral blood mononuclear cells stimulated with OKT3. The accumulated data indicate that PLIF is an embryonic immune factor involved in down-modulating the maternal immune recognition of the embryo toward anergy. This mechanism may have been adapted by breast cancer cells over expressing PLIF.
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PMID:PLIF, a novel human ferritin subunit from placenta with immunosuppressive activity. 1182 35

To isolate bovine oocyte marker genes, we performed suppressive and subtractive hybridization between oocytes and somatic tissues (i.e., intestine, lung, muscle, and cumulus cells). The subtracted library was characterized by sequencing 185 random clone inserts, representing 146 nonredundant genes. After Blast analysis within GenBank, 64% could be identified, 21% were homologous to unannotated expressed sequence tag (EST) or genomic sequences, and 15% were novel. Of 768 clone inserts submitted for differential screening by macroarray hybridization, 83% displayed a fourfold overexpression in the oocyte. The 40 most preferential nonredundant ESTs were submitted to GenBank analysis. Several well-known oocyte-specific genes were represented, including growth differentiation factor 9, bone morphogenetic protein 15, or the zona pellucida glycoprotein genes. Other ESTs were not identified. We investigated the expression profile of several candidates in the oocyte and a panel of gonadal and somatic tissues by reverse transcription-polymerase chain reaction. B-cell translocation gene 4, cullin 1, MCF.2 transforming sequence, a locus similar to snail soma ferritin, and three unidentified genes were, indeed, preferentially expressed in the oocyte, even though most were also highly expressed in testis. The transcripts were degraded throughout preimplantation development and were not compensated for by embryonic transcription after the morula stage. These profiles suggest a role in gametogenesis, fertilization, or early embryonic development.
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PMID:Genes preferentially expressed in bovine oocytes revealed by subtractive and suppressive hybridization. 1593 Mar 21

To identify genes associated with insulin-like growth factor-I receptor (IGF-IR)-mediated cellular transformation, we isolated genes that are differentially expressed in R- cells (derived from the IGF-IR knockout mouse) and R+ cells (R- cells that overexpress the IGF-IR). From these, 45 genes of known function were expressed at higher levels in R+ cells and 22 were expressed at higher levels in R- cells. Differential expression was confirmed by Northern blot analysis of R+ and R- cells. Genes expressed more abundantly in R+ cells are associated with (1) tumour growth and metastasis including, betaigH3, mts1, igfbp5 protease, and mystique; (2) cell division, including cyclin A1 and cdk1; (3) signal transduction, including pkcdeltabp and lmw-ptp; and (4) metabolism including ATPase H+ transporter and ferritin. In MCF-7 cells IGF-I induced expression of two genes, lasp-1 and mystique, which could contribute to metastasis. Lasp-1 expression required activity of the PI3-kinase signalling pathway. Mystique was highly expressed in metastatic but not in androgen-dependent prostate cancer cell lines and Mystique overexpression in MCF-7 cells promoted cell migration and invasion. We conclude that genes identified in this screen may mediate IGF-IR function in cancer progression.
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PMID:Gene expression profiles in cells transformed by overexpression of the IGF-I receptor. 1594 Feb 54

Cytoplasmic serine hydroxymethyltransferase (cSHMT) enzyme levels are elevated by the expression of the heavy chain ferritin (H ferritin) cDNA in cultured cells without corresponding changes in mRNA levels, resulting in enhanced folate-dependent de novo thymidylate biosynthesis and impaired homocysteine remethylation. In this study, the mechanism whereby H ferritin regulates cSHMT expression was determined. cSHMT translation is shown to be regulated by an H ferritin-responsive internal ribosome entry site (IRES) located within the cSHMT mRNA 5'-untranslated region (5'-UTR). The cSHMT 5'-UTR exhibited IRES activity during in vitro translation of bicistronic mRNA templates, and in MCF-7 and HeLa cells transfected with bicistronic mRNAs. IRES activity was depressed in H ferritin-deficient mouse embryonic fibroblasts and elevated in cells expressing the H ferritin cDNA. H ferritin was shown to interact with the mRNA-binding protein CUGBP1, a protein known to interact with the alpha and beta subunits of eukaryotic initiation factor eIF2. Small interference RNA-mediated depletion of CUGBP1 decreased IRES activity from bicistronic templates that included the cSHMT 3'-UTR in the bicistronic construct. The identification of this H ferritin-responsive IRES represents a mechanism that accounts for previous observations that H ferritin regulates folate metabolism.
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PMID:A ferritin-responsive internal ribosome entry site regulates folate metabolism. 1770 48

A methylene blue-encapsulated apoferritin complex shows cytotoxic effects on MCF-7 human breast adenocarcinoma cells when irradiated at the appropriate wavelength.
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PMID:Apoferritin protein cages: a novel drug nanocarrier for photodynamic therapy. 1881 89

This study reports that photosensitizers encapsulated in supramolecular protein cages can be internalized by tumor cells and can deliver singlet oxygen intracellularly for photodynamic therapy (PDT). As an alternative to other polymeric and/or inorganic nanocarriers and nanoconjugates, which may also deliver photosensitizers to the inside of the target cells, protein nanocages provide a unique vehicle of biological origin for the intracellular delivery of photosensitizing molecules for PDT by protecting the photosensitizers from reactive biomolecules in the cell membranes, and yet providing a coherent, critical mass of destructive power (by way of singlet oxygen) upon specific light irradiation for photodynamic therapy of tumor cells. As a model, we demonstrated the successful encapsulation of methylene blue (MB) in apoferritin via a dissociation-reassembly process controlled by pH. The resulting MB-containing apoferritin nanocages show a positive effect on singlet oxygen production, and cytotoxic effects on MCF-7 human breast adenocarcinoma cells when irradiated at the appropriate wavelength (i.e. 633 nm).
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PMID:Cellular uptake and photodynamic activity of protein nanocages containing methylene blue photosensitizing drug. 2013 13


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