Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serum RNase (ribonuclease) of normal persons and of patients with pancreatitis, carcinoma of pancreas, or other neoplasms was determined with poly(C) as substrate. Strikingly abnormal elevations occur in the serum RNase of patients with pancreatic cancer. There is no elevation in the serum RNase level of patients with pancreatitis. Average serum RNase values of 52 normal persons, 10 patients with pancreatitis, 30 patients with pancreatic cancer, 28 patients with breast cancer, 11 patients with lung cancer, 20 patients with colon cancer, six patients with stomach cancer, and four patients with liver cancer, respectively, were 104, 120, 383, 131, 173, 197, 194, and 152 units/ml of serum. Ninety percent of the patients with pancreatic cancer were above the level of 250 units of serum and 90% of all patients with varied cancers were below this level. In the presence of severe renal insufficiency, marked elevation of serum RNase was also observed. Serum RNase, because of its unique specificity, pancreatic origin, and its abnormal elevation in sera of patients with pancreatic cancer, serves as a reliable biochemical marker of carcinoma of the pancreas in the presence of normal renal function.
 ...
PMID:Elevated serum ribonuclease in patients with pancreatic cancer. 106 80

In addition to being regulated by a complex array of cis- and trans-acting factors, c-myc protooncogene expression may be modulated by antisense RNA transcripts. Our previous studies have determined that depletion of intracellular polyamines by alpha-difluoromethylornithine results in a marked decrease in the transcription of the human c-myc gene. Because of reports that antisense transcription occurs in the 5' and 3' regions of this gene, we used a genomic clone of the human c-myc gene to ascertain whether polyamine depletion might induce an antisense RNA transcript. These studies demonstrate that polyamine depletion of the human colon cancer cell line COLO 320 results in induction of an endogenous RNA transcript with high homology to the antisense strand of the second intervening sequence (PvuII-RsaI) of the c-myc gene. Furthermore, during such depletion, steady state levels of this transcript vary inversely to the sense direction c-myc RNA. RNase protection studies suggest that the antisense transcript may arise from a different gene locus than the c-myc gene. To further identify the origins of this RNA, a cDNA library was generated from size-selected RNA and screened with c-myc sequences. A 438-base pair cDNA was isolated with approximately 85% homology, to a 285-base region in the second intron of the c-myc gene. Computer homology analysis further reveals that a 120-base region within this cDNA also has approximately 85% homology to the antisense strands of a number of genes, including the growth-related genes, N-myc, p53, and thymidine kinase. These studies provide the initial characterization of an endogenous antisense RNA transcript which could influence cell growth by modulating the expression of c-myc and other genes.
 ...
PMID:Characterization of an endogenous RNA transcript with homology to the antisense strand of the human c-myc gene. 137 45

Intestinal trefoil factor (ITF) is a small peptide bearing the unique motif of intrachain disulfide bonds characteristic of the trefoil family. Previous work had localized expression of ITF primarily within goblet cells in the small and large bowel, making it a candidate gene for the study of the molecular basis of intestinal and goblet cell-specific gene expression. In order to study the regulation of ITF expression, we have cloned the rat ITF gene and sequenced 1.7 kilobases of the 5'-flanking region. RNase protection analysis demonstrated a single transcriptional start site. Various lengths of the 5'-flanking region were linked to the reporter gene luciferase and transfected into the colon cancer cell lines LS174T and Caco-2, representing, respectively, cells with and without goblet cell-like phenotype. Expression in the goblet cell-like LS174T colon cancer cell line was nearly 10-fold greater than expression in Caco-2 cells which exhibit columnar enterocyte-like phenotype. The pattern of goblet cell-associated selective transcription required only 153 base pairs of the rat ITF 5'-flanking sequence. Transfection of a construct of human growth hormone under the control of the rat ITF promoter in the N2 subclone of HT-29 cells demonstrated expression of the reporter gene only in those cells exhibiting a goblet cell phenotype as assessed by expression of immunoreactive mucin. These initial studies of the 5'-flanking region of the ITF gene demonstrate the presence of cis-regulatory elements capable of directing goblet cell specific expression.
 ...
PMID:Molecular cloning of the rat intestinal trefoil factor gene. Characterization of an intestinal goblet cell-associated promoter. 772 58

Epigenetic alterations in the genome of tumor cells have attracted considerable attention since the discovery of widespread alterations in DNA methylation of colorectal cancers over 10 years ago. However, the mechanism of these changes has remained obscure. el-Deiry and coworkers [el-Deiry, W. S., Nelkin, B. D., Celano, P., Yen, R. C., Falco, J. P., Hamilton, S. R. & Baylin, S. B. (1991) Proc. Natl. Acad. Sci. USA 88, 3470-3474], using a quantitative reverse transcription-PCR assay, reported 15-fold increased expression of DNA methyltransferase (MTase) in colon cancer, compared with matched normal colon mucosa, and a 200-fold increase in MTase mRNA levels compared with mucosa of unaffected patients. These authors suggested that increases in MTase mRNA levels play a direct pathogenetic role in colon carcinogenesis. To test this hypothesis, we developed a sensitive quantitative RNase protection assay of MTase, linear over three orders of magnitude. Using this assay on 12 colorectal carcinomas and matched normal mucosal specimens, we observed a 1.8- to 2.5-fold increase in MTase mRNA levels in colon carcinoma compared with levels in normal mucosa from the same patients. There was no significant difference between the normal mucosa of affected and unaffected patients. Furthermore, when the assay was normalized to histone H4 expression, a measure of S-phase-specific expression, the moderate increase in tumor MTase mRNA levels was no longer observed. These data are in contrast to the previously reported results, and they indicate that changes in MTase mRNA levels in colon cancer are nonspecific and compatible with other markers of cell proliferation.
 ...
PMID:Limited up-regulation of DNA methyltransferase in human colon cancer reflecting increased cell proliferation. 881 6

Lck protein is expressed in some colon carcinoma cell lines but its expression in colon cancer cells in vivo has not been clarified. LCK transcription is regulated from two distinct promoters and initiated exclusively from the downstream promoter in colon carcinoma cell lines in contrast to peripheral lymphocytes. We investigated the expression of the downstream promoter-initiated LCK transcript in 18 colorectal primary cancer and normal mucosae, and two hepatic metastases, using a RNase protection assay with the EcoRI-BglII fragment of human LCK cDNA, YT16. In normal tissues, only traces of the LCK transcript were detected. The expression of the LCK transcript was augmented in 3/18 cancer specimens. The relative level of the LCK transcript in the cancer tissue compared to the average value of normal adjacent tissue was 10-60 in 3 cases, and 3-10 in 7 cases. One hepatic metastasis expressed more LCK message than the primary lesion. Our results indicate that the LCK message is strongly expressed in some colorectal cancers.
 ...
PMID:Augmented expression of LCK message directed from the downstream promoter in human colorectal cancer specimens. 886 6

We have attempted to detect telomerase activity by Southern blot analysis using a digoxigenin labeled probe (5'-(CCCTTA)6CCCTAA-3') Telomerase activity was detected in all cancer cell lines that were tested, and:the lower limit for detection was 10(3) cells. Although telomerase activity was detected in colon cancer tissues, it was not found in adenoma or normal tissues. Telomerase activity was completely abrogated by heat and RNase treatment of the CHAPS extract. Our results demonstrate that this nonradioisotopic assay is safe and reliable for detecting telomerase activity in cancer cell lines and biopsy samples.
 ...
PMID:Nonradioisotopic telomeric repeat amplification protocol (TRAP) using digoxigenin labeled probe. 943 45

Insulin-like growth factor-I (IGF-I) is known as a potent mitogen for a variety of cell types, including colon cancer cell lines. The objective of this study was to determine the effect of IGF-I on cell death induced by cytotoxic agents actinomycin D (Act-D), lovastatin (LOV), and doxorubicin (DOX) in the MCLM mouse colon cancer cell line, and the mechanisms involved. Subconfluent monolayer MCLM cells were treated with IGF-I (25 ng/ml) for 12 h in serum-free media. Various concentrations of cytotoxic agents then were added to the cells that were incubated continually at 37 degrees C for 24 h. Cell survival was determined with the MTT (3-[4-5-dimenthylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay, which assesses mitochondrial function in living cells. The mRNA expression for multidrug resistance gene-1 (mdr-1), c-H-ras, and manganese superoxide dismutase (MnSOD) in cells treated with IGF-I was examined by Northern blot or RNase protection assays. The levels of p-glycoprotein, a drug efflux pump encoded by the mdr-1 gene, were assessed by Western immunoblotting. Results demonstrated that 1) IGF-I significantly inhibited the cell death and apoptosis of MCLM cells treated with Act-D, LOV, or DOX; 2) IGF-I increased mRNA expression for mdr-1, c-H-ras, and MnSOD; 3) the p-glycoproteins in cells treated with IGF-I or stably transfected with c-H-ras were elevated when compared with control. These results suggest that IGF-I protects MCLM cells against death induced by cytotoxic agents; this acquired drug resistance may be mediated by multiple mechanisms, including promoting expression of mdr-1, c-H-ras, and MnSOD; whereas, the p-glycoprotein level stimulated by IGF-I may result partly from the increase of c-H-ras in the cells.
 ...
PMID:Insulin-like growth factor-I promotes multidrug resistance in MCLM colon cancer cells. 952 72

Sodium butyrate causes alteration of colon cancer cell morphology and biology towards that of a more differentiated phenotype. The retinoblastoma gene encodes a nuclear phosphoprotein (pRb) present in a wide range of human cancer cell lines including colon cancer cell lines. pRB is synthesized throughout the cell cycle and phosphorylated in a phase specific manner: the predominant proteins in G0/G1 are the unphosphorylated species (110 kD) whereas phosphorylated pRb (112-114 kD) are in S and G2. 110 kD pRb binds transcription factors and prevents transcription of responsive genes such as the gene for thymidine kinase, which are expressed in late G1. The precise mechanisms controlling cell arrest are unknown, but recent data suggest that cyclin-dependent kinase inhibitors such as p16 may play a role. The aim of the present study was to assess the effect of sodium butyrate on cell cycle staging, thymidine kinase activity, phosphorylation of the pRb protein and expression of p16. We show that sodium butyrate treatment induces differentiation of LS174T colon cancer cells, inhibits thymidine kinase activity concomitantly with induction of pRb dephosphorylation, p16 transcription and cell cycle arrest at G0/G1. Initial dephosphorylation was observed 24 h after treatment of LS174T cells with sodium butyrate, whereas complete shift to the dephosphorylated form was observed 3 days after treatment. Induction of pRb dephosphorylation by sodium butyrate preceded inhibition of growth and the specific cell cycle arrest. RNase protection assay with a p16 specific riboprobe showed undetectable levels in proliferating cells to several fold increase in differentiated colonocytes. In conclusion, the results provide evidence for a specific cellular mechanism of butyrate induced growth arrest and differentiation of a colon cancer cell line.
 ...
PMID:Sodium butyrate induces retinoblastoma protein dephosphorylation, p16 expression and growth arrest of colon cancer cells. 982 7

Biliary glycoprotein (BGP, CD66a, or C-CAM-1) is a cell adhesion glycoprotein expressed in colon, liver, and hematopoietic tissues. Four major isoforms (a-d) of BGP are expressed in most epithelial tissues by alternative mRNA splicing from a single gene. Since BGP is down regulated in colon cancer and in premalignant colonic adenomas, it has been of interest to study its expression in other tumors. Using immunohistochemistry with a BGP specific antibody, and mRNA analysis by in situ hybridization, RNase protection, and RT-PCR, we show here that BGP is expressed to the same extent in both normal and malignant breast, demonstrating that BGP is not down regulated in breast cancer. In normal breast, BGP expression is confined to the apical surface of ductal and lobular epithelial cells, while in invasive carcinoma of the breast, BGP is expressed throughout the cytoplasm. In situ hybridization shows a specific pattern of BGP expression in both normal and malignant breast epithelium. RNase protection analysis confirms the immunohistochemistry results and shows no quantitative differences between normal and malignant breast. RT-PCR analysis agrees with these results and shows that only 3 of the 4 major isoforms (a, c, d) of BGP are expressed in normal and malignant breast. Since recent studies by Turbide et al (Cancer Res 57: 2781-2788, 1997) have shown that the ratio of murine BGP isoforms may affect tumor suppression in colonic cancer, it is proposed here that the isoform difference between human breast and colon may account for the observed lack of BGP down-regulation in breast vs colon cancer.
 ...
PMID:Expression of biliary glycoprotein (CD66a) in normal and malignant breast epithelial cells. 985 84

While colonoscopy may detect early-stage colon tumors, a less invasive and more cost-effective technique would be beneficial. Stool, which picks up sloughed-off colonic epithelial cells, would be ideal for sampling the mucosa; shed tumor cells may display alterations in gene expression observed in intact tumors. It is first necessary, however, to show that RNA can be isolated from human feces and that this RNA contains human gene transcripts. We have therefore developed a method for the isolation of total RNA from freshly passed human stool, consisting of lysis in chaotropic agents, repeated extraction with phenol and phenol-chloroform, and absorption with an RNA-binding resin. After treatment with RNase-free DNase I, we assayed these preparations for the presence of human RNA by quantitative slot blotting, northern blotting, and reverse transcription-polymerase chain reaction (RT-PCR). We obtained 5-30 microg RNA per gram of stool from cancer patients, and about 5 microg RNA per gram of control stool. Quantitative slot blotting showed that about 10% of this RNA was of human origin. Both northern blotting and RT-PCR demonstrated the presence of human RNA in these samples. To unambiguously demonstrate the isolation of RNA from stool, we incubated a mixture of rat cells and control human stool at 37 degrees C for up to 24 hr. RT-PCR of the RNA isolated from this sample clearly revealed the presence of rat-specific mRNA. These experiments indicate that RNA can be isolated from human stool and that message encoded by human genes can be assayed in these preparations. This procedure may provide a powerful tool to identify patients at risk for colon cancer.
 ...
PMID:Purification of total RNA from human stool samples. 988 97


1 2 3 Next >>