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)

Immunohistochemical staining for ferritin was performed on 11 human head and neck squamous cell carcinomas transplanted in nude mouse xenografts. Seven tumors were found to be positive. Using ferritin as a tumor antigen target, escalating doses of yttrium-90-labeled antiferritin antibodies were injected intravascularly into nude mice that were transplanted with a ferritin-positive human squamous cell carcinoma. Forty-five days after injection, the mean treated tumor size was 25.6% of control in the 100-microCi group, and 20.6% of control in the 200-microCi group. Ninety days after injection the mean tumor size was 27.5% that of control in the 100-microCi group and 31.7% in the 200-microCi group. Higher doses of radiation (300 and 400 microCi per mouse) caused death of most of the animals due to radiation toxicity. Presensitization of the animal, before antibody injection, with a bolus intraperitoneal injection of 7.5 mg of cisplatin per kilogram of body weight, resulted in further reduction in tumor size when compared with antibody alone or cisplatin alone. This study demonstrates that radioimmunotherapy with selected doses of yttrium-90-labeled antiferritin antibodies is effective against human head and neck squamous cell carcinoma xenografts in nude mice.
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PMID:Radiolabeled antibody therapy for squamous cell carcinoma of the head and neck. 835 16

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

Cytokines are implicated in the anaemia of chronic disease by reducing erythropoiesis and increasing iron sequestration in the reticuloendotheial system. However, the effect of cytokines, in particular TNFalpha (tumour necrosis factor alpha), on small bowel iron uptake and iron-transporter expression remains unclear. In the present study, we subjected CD1 male mice to intraperitoneal injection with TNFalpha (10 ng/mouse) and then examined the expression and localization of DMT1 (divalent metal transporter 1), IREG1 (iron-regulated protein 1) and ferritin in duodenum. Liver and spleen samples were used to determine hepcidin mRNA expression. Changes in serum iron and iron loading of duodenum, spleen and liver were also determined. We found a significant (P<0.05) fall in serum iron 3 h post-TNFalpha exposure. This was coincident with increased iron deposition in the spleen. After 24 h of exposure, there was a significant decrease in duodenal iron transfer (P<0.05) coincident with increased enterocyte ferritin expression (P<0.05) and re-localization of IREG1 from the basolateral enterocyte membrane. Hepatic hepcidin mRNA levels remained unchanged, whereas splenic hepcidin mRNA expression was reduced at 24 h. In conclusion, we provide evidence that TNFalpha may contribute to anaemia of chronic disease by iron sequestration in the spleen and by reduced duodenal iron transfer, which seems to be due to increased enterocyte iron binding by ferritin and a loss of IREG1 function. These observations were independent of hepcidin mRNA levels.
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PMID:Tumour necrosis factor alpha causes hypoferraemia and reduced intestinal iron absorption in mice. 1656 52

Bmp6 is the main activator of hepcidin, the liver hormone that negatively regulates plasma iron influx by degrading the sole iron exporter ferroportin in enterocytes and macrophages. Bmp6 expression is modulated by iron but the molecular mechanisms are unknown. Although hepcidin is expressed almost exclusively by hepatocytes (HCs), Bmp6 is produced also by non-parenchymal cells (NPCs), mainly sinusoidal endothelial cells (LSECs). To investigate the regulation of Bmp6 in HCs and NPCs, liver cells were isolated from adult wild type mice whose diet was modified in iron content in acute or chronic manner and in disease models of iron deficiency (Tmprss6 KO mouse) and overload (Hjv KO mouse). With manipulation of dietary iron in wild-type mice, Bmp6 and Tfr1 expression in both HCs and NPCs was inversely related, as expected. When hepcidin expression is abnormal in murine models of iron overload (Hjv KO mice) and deficiency (Tmprss6 KO mice), Bmp6 expression in NPCs was not related to Tfr1. Despite the low Bmp6 in NPCs from Tmprss6 KO mice, Tfr1 mRNA was also low. Conversely, despite body iron overload and high expression of Bmp6 in NPCs from Hjv KO mice, Tfr1 mRNA and protein were increased. However, in the same cells ferritin L was only slightly increased, but the iron content was not, suggesting that Bmp6 in these cells reflects the high intracellular iron import and export. We propose that NPCs, sensing the iron flux, not only increase hepcidin through Bmp6 with a paracrine mechanism to control systemic iron homeostasis but, controlling hepcidin, they regulate their own ferroportin, inducing iron retention or release and further modulating Bmp6 production in an autocrine manner. This mechanism, that contributes to protect HC from iron loading or deficiency, is lost in disease models of hepcidin production.
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PMID:Bmp6 expression in murine liver non parenchymal cells: a mechanism to control their high iron exporter activity and protect hepatocytes from iron overload? 2586 Aug 87