共查询到20条相似文献,搜索用时 46 毫秒
1.
Jeffrey E. Rubnitz Stephen J. Jacobsen Robert M. Hoffman 《Biochimica et Biophysica Acta (BBA)/General Subjects》1981,677(2):269-273
Methionine adenosyltransferase, one of the two major enzymes utilizing methionine, is regulated by the levels of methionine in the growth medium (Jacobsen, S.J., Hoffman, R.M. and Erbe, R.W. (1980) J. Natl. Cancer Inst. 65, 1237–1244, and Caboche, M. and Mulsant, P. (1978) Somatic Cell Genet. 4, 407–421). We report here that methionyl-tRNA synthetase, unlike methionine adenosyltransferase, behaves in a constitutive manner with respect to the concentration of methionine in the culture medium. This behavior is seen in Chinese hamster ovary cells and in normal diploid and SV 40-transformed human fibroblasts. Although the kinetics of regulation of methionine adenosyltransferase and methionyl-tRNA synthetase by exogenous methionine are clearly different, the levels of the two enzymes in the human cell lines are similar. 相似文献
2.
Park CS Cho K Bae DR Joo NE Kim HH Mabasa L Fowler AW 《In vitro cellular & developmental biology. Animal》2008,44(7):268-272
Lipotropes (methyl group containing nutrients, including methionine, choline, folate, and vitamin B(12)) are dietary methyl donors and cofactors that are involved in one-carbon metabolism, which is important for genomic DNA methylation reactions and nucleic acid synthesis. One-carbon metabolism provides methyl groups for all biological methylation pathways and is highly dependent on dietary supplementation of methyl nutrients. Nutrition is an important determinant of breast cancer risk and tumor behavior, and dietary intervention may be an effective approach to prevent breast cancer. Apoptosis is important for the regulation of homeostasis and tumorigenesis. The anti-apoptotic protein Bcl-2 may be a regulatory target in cancer therapy; controlling or modulating its expression may be a therapeutic strategy against breast cancer. In this study, the effects of lipotrope supplementation on the growth and death of human breast cancer cell lines T47D and MCF-7 were examined and found to inhibit growth of both T47D and MCF-7 cells. Furthermore, the ratios of apoptotic cells to the total number of cells were approximately 44% and 34% higher in the lipotrope-supplemented treatments of T47D and MCF-7 cancer cells, respectively, compared with the control treatments. More importantly, Bcl-2 protein expression was decreased by approximately 25% from lipotrope supplementation in T47D cells, suggesting that lipotropes can induce breast cancer cell death by direct downregulation of Bcl-2 protein expression. Cancer treatment failure is often correlated with Bcl-2 protein upregulation. These data may be useful in the development of effective nutritional strategies to prevent and reduce breast cancer in humans. 相似文献
3.
Unbalanced transmethylation and the perturbation of the differentiated state leading to cancer 总被引:2,自引:0,他引:2
R M Hoffman 《BioEssays : news and reviews in molecular, cellular and developmental biology》1990,12(4):163-166
It is proposed that the perturbation of the differentiated state in cancer is related to alterations in DNA methylation as well as to alterations in methylation of other cellular molecules, leading to an imbalance in global cellular methylation. It is hypothesized that the global imbalance in methylation is reflected in the enhanced levels of transmethylation seen in many cancer cell types as well as in a number of undermethylated molecules. 相似文献
4.
The novel cancer/testis antigen gene, NY-SAR-35, is expressed exclusively in normal testis and in various histological types
of tumor. However, the NY-SAR-35 gene expression is observed to be aberrant in several cancer cell lines and tissues. The
analysis of methylation status of the NY-SAR-35 gene promoter in various cancer cell lines showed that its expression was
related to methylation of the promoter region. Treatment of human cancer cell lines with the demethylating agent 5-aza-2′-deoxycytidine
activated the expression of the NY-SAR-35 gene. In addition, transfection experiments on various fragments of the CpG-rich
gene promoter indicate that in vitro methylation of the NY-SAR-35 gene promoter results in the loss of promoter activity.
The expression of NY-SAR-35 is therefore activated by hypomethylation of the CpG island in the gene promoter. 相似文献
5.
Summary Among the first nutrients to be linked to cancer were methyl group containing nutrients including methionine. Methionine and
its metabolic derivatives are essential components in several indispensable biological reactions including protein synthesis,
polyamine synthesis, and many transmethylation reactions. The purpose of this study was to determine the extent to which methionine
excess affects the proliferation and gene expression of the human breast cancer cell line MCF-7. Cells were first grown in
control medium; the medium was then replaced with either control or methionine-supplemented treatment media. We found that
5 and 10 g/L methionine significantly suppressed cell growth on day 1, and no further growth was detected after 3 d of treatment.
Cell, proliferation in the methionine treated group was significantly lower than that of the control group. Northern analysis
revealed that expression of p53 in methionine-treated MCF-7 cells was approximately 70% lower than that of control cells.
p53 is a key cell cycle regulatory, protein that has been implicated in tumorigenesis and cancer progression. Alteration of
the p53 tumor suppressor gene is the most common genetic change found in a wide variety of malignancies, including cancer.
This study shows that excess methionine (5 g/L) inhibited proliferation of MCF-7 breast cancer cells, and down regulation
of p53 is correlated with this inhibition. These findings may aid in the development of nutritional strategies for breast
cancer therapy. 相似文献
6.
Robert M. Hoffman 《In vitro cellular & developmental biology. Plant》1982,18(5):421-428
Summary Methionine dependence is a defect found in many cancer cell lines that inhibits their growth in culture when methionine is
replaced by its immediate precursor, homocysteine, in the culture medium. Normal cultured cells do not have this defect. This
report lists the diverse and large number of animal and human cancer lines that are methionine-dependent, and critically reviews
the cell biology and methionine biochemistry of the phenomenon.
This work was supported by Grant CA27564 from the National Institutes of Health; The Council for Tobacco Research-USA, Inc.;
The United Cancer Council, Inc.; The Cancer Research Coordinating Committee of the University of California; Grants from the
Academic Senate, University of California, San Diego; and a Special Fellowship to R. M. H. from the Leukemia Society of America.
An erratum to this article is available at . 相似文献
7.
Keith Booher Da-Wei Lin Stacey L. Borrego Peter Kaiser 《Cell cycle (Georgetown, Tex.)》2012,11(23):4414-4423
Methionine and homocysteine are metabolites in the transmethylation pathway leading to synthesis of the methyl-donor S-adenosylmethionine (SAM). Most cancer cells stop proliferating during methionine stress conditions, when methionine is replaced in the growth media by its immediate metabolic precursor homocysteine (Met-Hcy+). Non-transformed cells proliferate in Met-Hcy+ media, making the methionine metabolic requirement of cancer cells an attractive target for therapy, yet there is relatively little known about the molecular mechanisms governing the methionine stress response in cancer cells. To study this phenomenon in breast cancer cells, we selected methionine-independent-resistant cell lines derived from MDAMB468 breast cancer cells. Resistant cells grew normally in Met-Hcy+ media, whereas their parental MDAMB468 cells rapidly arrest in the G1 phase. Remarkably, supplementing Met-Hcy+ growth media with S-adenosylmethionine suppressed the cell proliferation defects, indicating that methionine stress is a consequence of SAM limitation rather than low amino acid concentrations. Accordingly, mTORC1 activity, the primary effector responding to amino acid limitation, remained high. However, we found that levels of the replication factor Cdc6 decreased and pre-replication complexes were destabilized in methionine-stressed MDAMB468 but not resistant cells. Our study characterizes metabolite requirements and cell cycle responses that occur during methionine stress in breast cancer cells and helps explain the metabolic uniqueness of cancer cells. 相似文献
8.
《Cell cycle (Georgetown, Tex.)》2013,12(23):4414-4423
Methionine and homocysteine are metabolites in the transmethylation pathway leading to synthesis of the methyl-donor S-adenosylmethionine (SAM). Most cancer cells stop proliferating during methionine stress conditions, when methionine is replaced in the growth media by its immediate metabolic precursor homocysteine (Met-Hcy+). Non-transformed cells proliferate in Met-Hcy+ media, making the methionine metabolic requirement of cancer cells an attractive target for therapy, yet there is relatively little known about the molecular mechanisms governing the methionine stress response in cancer cells. To study this phenomenon in breast cancer cells, we selected methionine-independent-resistant cell lines derived from MDAMB468 breast cancer cells. Resistant cells grew normally in Met-Hcy+ media, whereas their parental MDAMB468 cells rapidly arrest in the G1 phase. Remarkably, supplementing Met-Hcy+ growth media with S-adenosylmethionine suppressed the cell proliferation defects, indicating that methionine stress is a consequence of SAM limitation rather than low amino acid concentrations. Accordingly, mTORC1 activity, the primary effector responding to amino acid limitation, remained high. However, we found that levels of the replication factor Cdc6 decreased and pre-replication complexes were destabilized in methionine-stressed MDAMB468 but not resistant cells. Our study characterizes metabolite requirements and cell cycle responses that occur during methionine stress in breast cancer cells and helps explain the metabolic uniqueness of cancer cells. 相似文献
9.
Mariana Pavon-Eternod Suzanna Gomes Renaud Geslain Qing Dai Marsha Rich Rosner Tao Pan 《Nucleic acids research》2009,37(21):7268-7280
Increased proliferation and elevated levels of protein synthesis are characteristics of transformed and tumor cells. Though components of the translation machinery are often misregulated in cancers, what role tRNA plays in cancer cells has not been explored. We compare genome-wide tRNA expression in cancer-derived versus non-cancer-derived breast cell lines, as well as tRNA expression in breast tumors versus normal breast tissues. In cancer-derived versus non-cancer-derived cell lines, nuclear-encoded tRNAs increase by up to 3-fold and mitochondrial-encoded tRNAs increase by up to 5-fold. In tumors versus normal breast tissues, both nuclear- and mitochondrial-encoded tRNAs increase up to 10-fold. This tRNA over-expression is selective and coordinates with the properties of cognate amino acids. Nuclear- and mitochondrial-encoded tRNAs exhibit distinct expression patterns, indicating that tRNAs can be used as biomarkers for breast cancer. We also performed association analysis for codon usage-tRNA expression for the cell lines. tRNA isoacceptor expression levels are not geared towards optimal translation of house-keeping or cell line specific genes. Instead, tRNA isoacceptor expression levels may favor the translation of cancer-related genes having regulatory roles. Our results suggest a functional consequence of tRNA over-expression in tumor cells. tRNA isoacceptor over-expression may increase the translational efficiency of genes relevant to cancer development and progression. 相似文献
10.
《Epigenetics》2013,8(2):119-125
In cancer the extensive methylation found in the bulk of chromatin is reduced, while the normally unmethylated CpG islands become hypermethylated. Regions of solid tumors are transiently and/or chronically exposed to ischemia (hypoxia) and reperfusion, conditions known to contribute to cancer progression. We hypothesized that hypoxic microenvironment may influence local epigenetic alterations, leading to inappropriate silencing and re-awakening of genes involved in cancer. We cultured human colorectal and melanoma cancer cell lines under severe hypoxic conditions, and examined their levels of global methylation using HPLC to quantify 5-methylcytosine (5-mC), and found that hypoxia induced losses of global methylation. This was more extensive in normal human fibroblasts than cancer cell lines. Cell lines from metastatic colorectal carcinoma or malignant melanoma were found to be markedly more hypomethylated than cell lines from their respective primary lesions, but they did not show further reduction of 5-mC levels under hypoxic conditions. To explore these epigenetic changes in vivo, we established xenografts of the same cancer cells in immune deficient mice. We used Hypoxyprobe? to assess the magnitude of tissue hypoxia, and immunostaining for 5-mC to evaluate DNA methylation status in cells from different regions of tumors. We found an inverse relationship between the presence of extensive tumor hypoxia and the incidence of methylation, and a reduction of 5-mC in xenografts compared to the levels seen in the same cancer cell lines in vitro, verifying that methylation patterns are also modulated by hypoxia in vivo. This suggests that epigenetic events in solid tumors may be modulated by microenvironmental conditions such as hypoxia. 相似文献
11.
I-Hsuan Lin Dow-Tien Chen Yi-Feng Chang Yu-Ling Lee Chia-Hsin Su Ching Cheng Yi-Chien Tsai Swee-Chuan Ng Hsiao-Tan Chen Mei-Chen Lee Hong-Wei Chen Shih-Hui Suen Yu-Cheng Chen Tze-Tze Liu Chuan-Hsiung Chang Ming-Ta Hsu 《PloS one》2015,10(2)
Oncogenic transformation of normal cells often involves epigenetic alterations, including histone modification and DNA methylation. We conducted whole-genome bisulfite sequencing to determine the DNA methylomes of normal breast, fibroadenoma, invasive ductal carcinomas and MCF7. The emergence, disappearance, expansion and contraction of kilobase-sized hypomethylated regions (HMRs) and the hypomethylation of the megabase-sized partially methylated domains (PMDs) are the major forms of methylation changes observed in breast tumor samples. Hierarchical clustering of HMR revealed tumor-specific hypermethylated clusters and differential methylated enhancers specific to normal or breast cancer cell lines. Joint analysis of gene expression and DNA methylation data of normal breast and breast cancer cells identified differentially methylated and expressed genes associated with breast and/or ovarian cancers in cancer-specific HMR clusters. Furthermore, aberrant patterns of X-chromosome inactivation (XCI) was found in breast cancer cell lines as well as breast tumor samples in the TCGA BRCA (breast invasive carcinoma) dataset. They were characterized with differentially hypermethylated XIST promoter, reduced expression of XIST, and over-expression of hypomethylated X-linked genes. High expressions of these genes were significantly associated with lower survival rates in breast cancer patients. Comprehensive analysis of the normal and breast tumor methylomes suggests selective targeting of DNA methylation changes during breast cancer progression. The weak causal relationship between DNA methylation and gene expression observed in this study is evident of more complex role of DNA methylation in the regulation of gene expression in human epigenetics that deserves further investigation. 相似文献
12.
Hong Zhao Jinmin Zhu Kemi Cui Xiaoyin Xu Megan O'Brien Kelvin K Wong Santosh Kesari Weiming Xia Stephen TC Wong 《Cancer cell international》2009,9(1):15
Background
Cancer and Alzheimer's disease (AD) are two seemingly distinct diseases and rarely occur simultaneously in patients. To explore molecular determinants differentiating pathogenic routes towards AD or cancer, we investigate the role of amyloid β protein (Aβ) on multiple tumor cell lines that are stably expressing luciferase (human glioblastoma U87; human breast adenocarcinoma MDA-MB231; and mouse melanoma B16F). 相似文献13.
Nino Sorgente Jon C. Bowersox 《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》1984,805(3):306-311
In a previous report (Bowersox, J.C. and Sorgente, N. (1982) Cancer Res. 42, 2547–2551) we demonstrated that the glycoprotein fibronectin is a chemoattractant for vascular endothelial cells. In probing the mechanisms by which fibronectin induces endothelial cell chemotaxis, we have discovered that the carboxy-O-methylation of cellular proteins is stimulated by fibronectin. By measuring the incorporation of l-[methyl-3H]methionine into alkali-labile, [3H]methyl ester linkages, we determined that fibronectin stimulated protein carboxy-O-methylation in aortic endothelial cells in a time- and concentration-dependent manner; the greatest stimulation occurred at 100 μg/ml fibronectin (approx. 35% above controls). When inhibitors of carboxymethylation were added, fibronectin-induced stimulation of protein methylation did not occur. Furthermore, inhibitors of methylation prevented the chemotaxis of endothelial cells in response to fibronectin. These data support our hypothesis that fibronectin mediates endothelial cell chemotaxis, such as that occurring during neovascularization. As carboxy-O-methylation of cell proteins is also effected by fibronectin, transmethylation reactions may be an important component of endothelial cell chemotaxis. 相似文献
14.
Studies designed to identify novel methylation events related to cancer often employ cancer cell lines in the discovery phase of the experiments and have a relatively low rate of discovery of cancer-related methylation events. An alternative algorithm for discovery of novel methylation in cancer uses primary tumor-derived xenografts instead of cell lines as the primary source of nucleic acid for evaluation. We evaluated DNA extracted from primary head and neck squamous cell carcinomas (HNSCC), xenografts grown from these primary tumors in nude mice, HNSCC-derived cell lines, normal oral mucosal samples, and minimally transformed oral keratinocyte-derived cell lines using Illumina Infinum Humanmethylation 27 genome-wide methylation microarrays. We found >2,200 statistically significant methylation differences between cancer cell lines and primary tumors and when comparing normal oral mucosa to keratinocyte cell lines. We found no statistically significant promoter methylation differences between primary tumor xenografts and primary tumors. This study demonstrates that tumor-derived xenografts are highly accurate representations of promoter methylation in primary tumors and that cancer derived cell lines have significant drawbacks for discovery of promoter methylation alterations in primary tumors. These findings also support use of primary tumor xenografts for the study of methylation in cancer, drug discovery, and the development of personalized cancer treatments. 相似文献
15.
Copy number changes and DNA methylation alterations are crucial to gene regulation in mammals. Recently, a number of microarray studies have been based on copy number and DNA methylation alterations in order to find clinical biomarkers of carcinogenesis. In this study, we attempted to combine profiles of copy number and methylation patterns in four human cancer cell lines using BAC microarray-based approaches and we detected several clinically important genes which showed genetic and epigenetic relationships. Within the clones analyzed, many contained cancer-related genes involved in cell cycle regulation, cell division, signal transduction, tumor necrosis, cell differentiation, and cell proliferation. One clone included the FHIT gene, a well-known tumor suppressor gene involved in various human cancers. Our combined profiling techniques may provide a method by which to find new clinicopathologic cancer biomarkers, and support the idea that systematic characterization of the genetic and epigenetic events in cancers may rapidly become a reality. 相似文献
16.
Raymond Gantt Frida Montes De Oca Virgina J. Evans 《In vitro cellular & developmental biology. Plant》1973,8(4):288-294
Summary Comparisons of nucleic acid methylation between paired neoplastic and non-neoplastic mouse cell lines have shown a striking
difference in the deoxyribonucleic acid (DNA) peak eluted from methylated albumin-kieselguhr columns (R. Gantt and V. J. Evans,
1969, Cancer Res. 29: 536–541). Since mouse satellite DNA is relatively highly methylated, its 5-methylcytosine content was
compared with mainband DNA in these two paired cell lines to determine whether this might account for the observed differences.
The cell DNA was labeled with methyl-labeled methionine and isolated from the cells by repeated neutral cesium chloride isopycnic
centrifugation. The satellite DNA strands were then separated in an alkaline cesium chloride gradient. Both the 5-methylcytosine
content and the relative amounts of satellite DNA were indistinguishable in the paired cell lines. Further, the results showed
that both strands of satellite DNA had virtually equal amounts of 5-methylcytosine, although the heavy strand contains 1.5
times more cytosine than the light strand. 相似文献
17.
Methylthioadenosine phosphorylase gene expression is impaired in human liver cirrhosis and hepatocarcinoma 总被引:3,自引:0,他引:3
Berasain C Hevia H Fernández-Irigoyen J Larrea E Caballería J Mato JM Prieto J Corrales FJ García-Trevijano ER Avila MA 《Biochimica et biophysica acta》2004,1690(3):276-284
Methylthioadenosine phosphorylase (MTAP) is a key enzyme in the methionine and adenine salvage pathways. In mammals, the liver plays a central role in methionine metabolism, and this essential function is lost in the progression from liver cirrhosis to hepatocarcinoma. Deficient MTAP gene expression has been recognized in many transformed cell lines and tissues. In the present work, we have studied the expression of MTAP in human and experimental liver cirrhosis and hepatocarcinoma. We observe that MTAP gene expression is significantly reduced in human hepatocarcinoma tissues and cell lines. Interestingly, MTAP gene expression was also impaired in the liver of CCl4-cirrhotic rats and cirrhotic patients. We provide evidence indicating that epigenetic mechanisms, involving DNA methylation and histone deacetylation, may play a role in the silencing of MTAP gene expression in hepatocarcinoma. Given the recently proposed tumor suppressor activity of MTAP, our observations can be relevant to the elucidation of the molecular mechanisms of multistep hepatocarcinogenesis. 相似文献
18.
19.
D S Swafford S K Middleton W A Palmisano K J Nikula J Tesfaigzi S B Baylin J G Herman S A Belinsky 《Molecular and cellular biology》1997,17(3):1366-1374
The p16INK4a (p16) tumor suppressor gene is frequently inactivated by homozygous deletion or methylation of the 5' CpG island in cell lines derived from human non-small-cell lung cancers. However, the frequency of dysfunction in primary tumors appears to be significantly lower than that in cell lines. This discordance could result from the occurrence or selection of p16 dysfunction during cell culture. Alternatively, techniques commonly used to examine tumors for genetic and epigenetic alterations may not be sensitive enough to detect all dysfunctions within the heterogeneous cell population present in primary tumors. If p16 inactivation plays a central role in development of non-small-cell lung cancer, then the frequency of gene inactivation in primary tumors should parallel that observed in cell lines. The present investigation addressed this issue in primary rat lung tumors and corresponding derived cell lines. A further goal was to determine whether the aberrant p16 gene methylation seen in human tumors is a conserved event in this animal model. The rat p16 gene was cloned and sequenced, and the predicted amino acid sequence of its product found to be 62% homologous to the amino acid sequence of the human analog. Homozygous deletion accounted for loss of p16 expression in 8 of 20 cell lines, while methylation of the CpG island extending throughout exon 1 was observed in 9 of 20 cell lines. 2-Deoxy-5-azacytidine treatment of cell lines with aberrant methylation restored gene expression. The methylated phenotype seen in cell lines showed an absolute correlation with detection of methylation in primary tumors. Aberrant methylation was also detected in four of eight primary tumors in which the derived cell line contained a deletion in p16. These results substantiate the primary tumor as the origin for dysfunction of the p16 gene and implicate CpG island methylation as the major mechanism for inactivating this gene in the rat lung tumors examined. Furthermore, rat lung cancer appears to be an excellent model in which to investigate the mechanisms of de novo gene methylation and the role of p16 dysfunction in the progression of neoplasia. 相似文献