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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Choline is an essential nutrient participating as the initial substrate in major metabolic pathways. The differential metabolic routing of choline was investigated in MCF7 human breast cancer implanted in nude mice and in the kidney, liver, and brain of these mice. The distribution of metabolites following infusion of [1,2-(13)C]-choline was monitored by (13)C magnetic resonance spectroscopy. This infusion led to an 18-fold increase in plasma choline and to concomitant changes in the content and distribution of choline metabolites. In vivo kinetic studies of the tumor during the infusion demonstrated accumulation of choline in the interstitium and intracellular synthesis of phosphocholine. The amount of unlabeled choline metabolites was 7.1, 4.1, 3.5, and 1.4 micromol/g in the kidney, liver, tumor, and brain, respectively. The variations in the labeled metabolites were more pronounced with high amounts in the kidney and liver (8.0 and 4.3 micromol/g, respectively) and very low amounts in the tumor and brain (0.33 and 0.12 micromol/g, respectively). In the kidney and liver, betaine (unlabeled and labeled) was the predominant choline metabolite. The dominant unlabeled metabolite in breast cancer was phosphocholine and in the brain glycerophosphocholine. Magn Reson Med 46:31-38, 2001.
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PMID:Differential routing of choline in implanted breast cancer and normal organs. 1144 8

Specific genetic alterations during malignant transformation may induce the synthesis and breakdown of choline phospholipids, mediating transduction of mitogenic signals. The high level of water-soluble choline metabolites in cancerous breast tumors, relative to benign lesions and normal breast tissue, has been used as a diagnostic marker of malignancy. To unravel the biochemical pathways underlying this phenomenon, we used tracer kinetics and 13C and 31P magnetic resonance spectroscopy to compare choline transport, routing, and metabolism to phospholipids in primary cultures of human mammary epithelial cells and in MCF7 human breast cancer cells. The rate of choline transport under physiological choline concentrations was 2-fold higher in the cancer cells. The phosphorylation of choline to phosphocholine and oxidation of choline to betaine yielded 10-fold higher levels of these metabolites in the cancer cells. However, additional incorporation of choline to phosphatidylcholine was similar in both cell types. Thus, enhanced choline transport and augmented synthesis of phosphocholine and betaine are dominant pathways responsible for the elevated presence of choline metabolites in cancerous breast tumors. Uniquely, reduced levels and synthesis of a choline-ether-phospholipid may also serve as a metabolic marker of breast cancer.
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PMID:Metabolic markers of breast cancer: enhanced choline metabolism and reduced choline-ether-phospholipid synthesis. 1192 12

Folate, vitamin B6, vitamin B12, methionine, choline, and betaine are nutrients involved in one-carbon metabolism and have been hypothesized to reduce the risk of breast cancer. However, previous epidemiologic studies on most of these nutrients and breast cancer risk have been inconclusive and have included primarily postmenopausal women. No study has examined choline and betaine in relation to breast cancer risk. Therefore, we examined the intake of these nutrients in relation to breast cancer risk among 90,663 premenopausal women ages 26 to 46 years in 1991 in the Nurses' Health Study II. Nutrient intake was assessed with a validated food frequency questionnaire in 1991, 1995, and 1999. During 12 years of follow-up from 1991 to 2003, we documented 1,032 incident cases of invasive breast cancer. Overall, none of the nutrients was associated with risk of breast cancer. The results were similar by levels of alcohol intake and folate intake and for estrogen receptor-negative breast cancer. In conclusion, we found no evidence that higher intakes of nutrients involved in one-carbon metabolism reduce risk of breast cancer among premenopausal women.
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PMID:Nutrients involved in one-carbon metabolism and risk of breast cancer among premenopausal women. 1808 90

Choline is an essential nutrient required for methyl group metabolism, but its role in carcinogenesis and tumor progression is not well understood. By utilizing a population-based study of 1508 cases and 1556 controls, we investigated the associations of dietary intake of choline and two related micronutrients, methionine and betaine, and risk of breast cancer. The highest quintile of choline consumption was associated with a lower risk of breast cancer [odds ratio (OR): 0.76; 95% confidence interval (CI): 0.58-1.00] compared with the lowest quintile. Two putatively functional single nucleotide polymorphisms of choline-metabolizing genes, PEMT -774G>C (rs12325817) and CHDH +432G>T (rs12676), were also found be related to breast cancer risk. Compared with the PEMT GG genotype, the variant CC genotype was associated with an increased risk of breast cancer (OR: 1.30; 95% CI: 1.01-1.67). The CHDH minor T allele was also associated with an increased risk (OR: 1.19; 95% CI: 1.00-1.41) compared with the major G allele. The BHMT rs3733890 polymorphism was also examined but was found not to be associated with breast cancer risk. We observed a significant interaction between dietary betaine intake and the PEMT rs7926 polymorphism (P(interaction)=0.04). Our findings suggest that choline metabolism may play an important role in breast cancer etiology.
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PMID:Choline metabolism and risk of breast cancer in a population-based study. 1823 Jun 80

Choline oxidation to betaine takes place in the mitochondria; however, a protein regulating mitochondrial choline transport was never identified. The purpose of this study was to analyze subcellular localization of the solute carrier 44A1 (SLC44A1), a plasma membrane choline transporter sensitive to inhibition by hemicholinium-3. We generated N- and C-terminal-SLC44A1-specific antibodies and analyzed localization of endogenous and overexpressed SLC44A1 in C2C12 mouse muscle cells, MCF7 human breast cancer cells, and mouse tissues using confocal microscopy, differential centrifugation, and Western blotting. We further performed choline uptake competition studies on isolated mitochondria using the specific inhibitor hemicholinium-3 and SLC44A1 antibodies, and analyzed mitochondria of FL83B hepatocytes after the targeted knock-down of SLC44A1 using siRNA technology. In addition, we analyzed SLC44A1 expression during choline deficiency. Localization studies revealed plasma membrane, cytosolic, microsomal, and mitochondrial localization of endogenous and His-tagged SLC44A1. Uptake studies in isolated mitochondria show an accumulation of (3)H-choline, which is strongly inhibited by hemicholinium-3 (60%), by an excess of unlabeled choline (97%), and by both SLC44A1 antibodies. SLC44A1 mRNA and protein expression were down-regulated during choline deficiency. These data clearly establish SLC44A1 as an important mediator of choline transport across both the plasma membrane and the mitochondrial membrane.
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PMID:The solute carrier 44A1 is a mitochondrial protein and mediates choline transport. 1935 33

Choline and betaine provide methyl groups for one-carbon metabolism. Humans obtain these nutrients from a wide range of foods. Betaine can also be synthesized endogenously from its precursor, choline. Although animal studies have implied a causal relationship between choline deficiency and carcinogenesis, the role of these two nutrients in human carcinogenesis and tumor progression is not well understood. We investigated the associations of dietary intakes of choline and betaine and breast cancer risk and mortality in the population-based Long Island Breast Cancer Study Project. Among the 1508 case-group women, 308 (20.2%) deaths occurred, among whom 164 (53.2%) died of breast cancer by December 31, 2005. There was an indication that a higher intake of free choline was associated with reduced risk of breast cancer (P(trend)=0.04). Higher intakes of betaine, phosphocholine, and free choline were associated with reduced all-cause as well as breast cancer-specific mortality in a dose-dependent fashion. We also explored associations of polymorphisms of three key choline- and betaine-metabolizing genes and breast cancer mortality. The betaine-homocysteine methyltransferase gene (BHMT) rs3733890 polymorphism was associated with reduced breast cancer-specific mortality (hazard ratio, 0.64; 95% confidence interval, 0.42-0.97). Our study supports the important roles of choline and betaine in breast carcinogenesis. It suggests that high intake of these nutrients may be a promising strategy to prevent the development of breast cancer and to reduce its mortality.
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PMID:High intakes of choline and betaine reduce breast cancer mortality in a population-based study. 1963 52

Recent human studies found that the mRNA expression level of aryl-hydrocarbon receptor nuclear translocator 2 (ARNT2) was positively associated with the prognosis of breast cancer. In this study, we used small interfering RNA techniques to knockdown ARNT2 expression in MCF7 human breast cancer cells, and found that an almost 40% downregulation of ARNT2 mRNA expression increased the expression of sensitive to apoptosis gene (3.36-fold), and decreased the expression of von Hippel-Lindau (0.27-fold) and matrix metalloproteinase-1 (0.35-fold). The metabolite analysis revealed the contents of glucose, glycine, betaine, phosphocholine, pyruvate and lactate involved in the hypoxia-inducible factor (HIF)-1-dependent glycolytic pathway were significantly lower in cells treated with siARNT2. Our results suggested that ARNT2 might play an important role in the modulation of HIF-1-regulated signaling and metabolism.
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PMID:siRNA-mediated knockdown of aryl hydrocarbon receptor nuclear translocator 2 affects hypoxia-inducible factor-1 regulatory signaling and metabolism in human breast cancer cells. 2194 17

Few epidemiological studies have evaluated the association of choline and betaine intake with breast cancer risk and the results remain inconsistent. This study aimed to assess the relationship between dietary intake of choline and betaine and the risk of breast cancer among Chinese women. A two-stage case-control study was conducted, with 807 cases and 807 age- (5-year interval) and residence (rural/urban)-matched controls. A validated food frequency questionnaire was used to assess dietary intake by face-to-face interview. An unconditional logistic regression model was used to calculate multivariate-adjusted odds ratios (OR) and 95% confidence intervals (CI). A significant inverse association was found between dietary choline and betaine consumption and breast cancer risk. The adjusted OR for the highest quartile of intake compared with the lowest were 0.40 (95% CI = 0.28-0.57, P(trend) < 0.001) for total choline intake, 0.58 (95% CI = 0.42-0.80, P(trend) < 0.001) for betaine intake and 0.38 (0.27-0.53, P(trend) < 0.001) for choline plus betaine intake, respectively. Intakes of individual choline compouds, choline from glycerophosphocholine, phosphocholine, phosphatidylcholine, sphingomyelin and free choline were also negatively associated with breast cancer risk. The inverse association between choline intake and breast cancer risk was primarily confined to participants with low folate level (<242 g/day), with an OR (95% CI) of 0.46 (0.23-0.91) comparing the fourth quartile with the first quartile of choline intake (P(trend) = 0.005). The present study suggests that consumption of choline and betaine is inversely associated with the risk of breast cancer. The association of choline intake with breast cancer risk is probably modified by folate intake.
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PMID:Choline and betaine intake is inversely associated with breast cancer risk: a two-stage case-control study in China. 2314 May 34

Vanadium is known for its antitumorigenicity. Poised to investigate the impact of well-defined forms of vanadium on processes and specific biomolecules (oncogenes-proteins) involved in cancer cell physiology, a novel ternary V(V)-peroxido-betaine compound was employed in experiments targeting cell viability, apoptosis, reactive oxygen species (ROS) production, H-ras signaling, and matrix metalloproteinase-2 (MMP-2) expression in human breast cancer epithelial and lung adenocarcinoma cells. The results reveal that vanadium imparts a significant decrease in cancer cell viability, reducing H-ras and MMP-2 expression by increasing ROS-mediated apoptosis, distinctly emphasizing the nature, structure and properties of ternary ligands on vanadium anti-tumor activity and its future potential as a metallodrug.
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PMID:Novel ternary vanadium-betaine-peroxido species suppresses H-ras and matrix metalloproteinase-2 expression by increasing reactive oxygen species-mediated apoptosis in cancer cells. 2347 96

Human choline dehydrogenase (CHD) is located in the inner membrane of mitochondria primarily in liver and kidney and catalyzes the oxidation of choline to glycine betaine. Its physiological role is to regulate the concentrations of choline and glycine betaine in the blood and cells. Choline is important for regulation of gene expression, the biosynthesis of lipoproteins and membrane phospholipids and for the biosynthesis of the neurotransmitter acetylcholine; glycine betaine plays important roles as a primary intracellular osmoprotectant and as methyl donor for the biosynthesis of methionine from homocysteine, a required step for the synthesis of the ubiquitous methyl donor S-adenosyl methionine. Recently, CHD has generated considerable medical attention due to its association with various human pathologies, including male infertility, homocysteinuria, breast cancer and metabolic syndrome. Despite the renewed interest, the biochemical characterization of the enzyme has lagged behind due to difficulties in the obtainment of purified, active and stable enzyme. This review article summarizes the medical relevance and the physiological roles of human CHD, highlights the biochemical knowledge on the enzyme, and provides an analysis based on the comparison of the protein sequence with that of bacterial choline oxidase, for which structural and biochemical information is available.
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PMID:Human choline dehydrogenase: medical promises and biochemical challenges. 2390 61


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