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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A human colon cancer cell line CaCo-2 differentiates spontaneously by expressing enterocytic phenotypes after the confluence of the culture. The authors examined a production of secretory components (SC) by CaCo-2 in relation to its differentiation. The SC production showed an increase immediately after the cells came to confluence, and reached its peak production during the 6th to the 9th day after confluence of the culture. SC production decreased remarkably after the 10th day. On the other hand, the activity of alkaline phosphatase of CaCo-2 showed a gradual increase up to the 18th day after confluence. The production of SC was not affected by the presence of dimeric IgA in the culture. Interferon-gamma enhanced SC production of CaCo-2 with dose-dependent manner. These observations indicate that capability of SC production of CaCo-2 is enhanced in the early stage of differentiation but is reduced in the late stage. Moreover, CaCo-2 provides a useful model for studying the regulation of SC production in enterocytic differentiation.
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PMID:The human colon cancer cell line CaCo-2 produces secretory components during enterocytic differentiation. 837 26

Elevated expression of the c-myc oncogene is a frequent finding in tumors and cell lines derived from carcinomas of the colon and rectum. In a previous study we demonstrated that the differentiation agent sodium butyrate causes a rapid reduction in the expression of c-myc RNA in the rectal carcinoma cell line SW837. This effect was blocked by inhibitors of protein synthesis, suggesting that butyrate causes the induction of an activity that has a negative effect on c-myc expression. In the present work we demonstrate that the rapid decrease in the level of c-myc RNA, upon treatment of SW837 cells with 2 mM butyrate, is followed by a slower decrease in the level of p53 RNA and an increase in the RNA levels for fibronectin and a placental type alkaline phosphatase. Using in vitro elongation of nascent transcripts to measure transcription and actinomycin D chase experiments to measure RNA stability, we show that the reduction in expression of c-myc RNA is due to an increase in the block to transcriptional elongation, rather than a decrease in transcriptional initiation or an increase in degradation of the RNA. We conclude that sodium butyrate induces an activity that increases the transcriptional block in SW837 cells, and that regulation of transcriptional elongation is an important mechanism for regulating c-myc expression in this cell type. A shift in relative usage of the two major promoters in the c-myc gene accompanies the reduction in expression. The potential significance of this finding with respect to transcriptional elongation is discussed. Mutations in the exon 1/intron 1 boundary region of the c-myc gene cause an increase in transcriptional elongation in Burkitt lymphoma. We sequenced this region in a series of cell lines derived from colorectal carcinomas, all of which had an elevated level of c-myc expression, to determine if a similar mutational mechanism is at work in this disease. All of the lines examined had a normal c-myc DNA sequence, suggesting that the deregulation of c-myc expression in colon cancer is not due to a cis mutation in this region.
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PMID:Sodium butyrate causes an increase in the block to transcriptional elongation in the c-myc gene in SW837 rectal carcinoma cells. 837 1

We examined the alterations of proliferative activity and c-myc expression of a colon cancer cell line (Caco-2) during its spontaneous differentiation. Caco-2 cells were cultured in various types of media and the degree of differentiation was monitored in terms of dome formation in cell monolayers and expression of alkaline phosphatase (ALP) activity. In Caco-2 cells cultured with Eagle's minimum essential medium (EMEM) containing 10% fetal calf serum (FCS), dome formation was demonstrated and ALP activity was markedly increased after the cells reached confluence. Five-fold reduction of c-myc mRNA and a marked decrease in S-phase cells were observed in the differentiated cells. These changes were not induced in FCS-free EMEM. The addition of insulin and transferrin to FCS-free EMEM did not induce cell differentiation or reduction of c-myc mRNA expression. When Caco-2 cells were cultured with three different serum-free media, the induction of dome formation and the increase of ALP activity were observed to varying degrees. Expression of c-myc mRNA in the cells cultured with one serum-free medium decreased to a level similar to that in fully differentiated cells cultured with EMEM containing 10% FCS. These results suggest that a spontaneous switch from a proliferative state with high c-myc expression to differentiated phenotype occurs after cells reach confluence and depends on the culture conditions.
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PMID:Changes of proliferative activity and phenotypes in spontaneous differentiation of a colon cancer cell line. 839 33

The human colon cancer cell line SW-620 produces two alkaline phosphatases (ALPs) which are not expressed by normal colon. They are the heat-stable, term-placental and the heat-labile, L-homoarginine-sensitive, liver/bone/kidney ALPs. Butyrate, an ALP inducer, has strikingly dissimilar effects on the activity of these enzymes: whereas high (2.0 mM) butyrate concentrations exclusively induce increased activity levels of liver/bone/kidney ALP, low (0.5 mM) concentrations increase the activity of both, albeit induction of term-placental ALP is less pronounced. These observations indicate that the effect of butyrate on the two ALPs is non-coordinate and suggest that their expression by SW-620 cells is independently modulated.
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PMID:Divergent effects of butyrate on the alkaline phosphatases of SW-620 cells. 842 35

In the present study we have determined membrane, cytosolic, and cytoskeleton-associated tyrosine protein kinase (TPK) activity in human colon cancer cell lines exposed to (i) the differentiation-promoting agents sodium butyrate and 8-chloro-cyclic-adenosine 3',5'-monophosphate (8-Cl-cAMP), (ii) tyrphostins, specific TPK inhibitors, or (iii) differentiation-inducing culture manipulations. Treatment of human colon cancer cell lines, LS 174T, COLO 205, and SW620, with sodium butyrate and 8-Cl-cAMP or tyrphostins AG-30 and AG-34, significantly attenuated TPK activity concomitantly with an increase in the activity of alkaline phosphatase, an enzymatic marker of intestinal cell differentiation. The differentiated phenotype induced in Caco-2 and HT-29 colon cancer cells by culture manipulation was associated with a significant decrease in cytoskeleton-associated TPK activity and marked activity of alkaline phosphatase (AP). Electron microscopy and freeze-fracturing analysis of HT-29 cells showed that the gradual transition from the undifferentiated to the differentiated phenotype resulted in the acquisition of a distinct polarized morphology. Immunocytochemical phosphotyrosine analysis of cultured SW620 cells showed positive staining mostly localized in zones of focal contacts. A marked reduction in phosphotyrosine staining with notable changes in cell morphology was observed in SW620 cells exposed to tyrphostins. Cumulatively, the present results indicate that the induction of the differentiated phenotype in colon cancer cells is associated with a marked decrease in TPK activity and tyrosine phosphorylation.
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PMID:Induction of the differentiated phenotype in human colon cancer cell is associated with the attenuation of subcellular tyrosine phosphorylation. 852 62

A human colon carcinoma cell line designated OUMS-23 has been established from metastatic pericardial fluid of a male familial adenomatous polyposis patient with colon cancer. Since 1984, the epithelial cells have been maintained in culture. Ultrastructural studies revealed the presence of numerous microvilli on the cell surface and desmosomes between the adjacent cells. The cells secreted carcinoembryonic antigen into the culture medium (15 ng/10(6) cells-1 24 h-1). The cells expressed heat-stable placental-type-like alkaline phosphatase, whereas the normal counterparts expressed tissue-unspecific alkaline phosphatase. Karyotypic analysis showed that the cell line was of human origin and that the chromosome number was broadly distributed between 53 and 118. Southern blot analysis of the APC gene revealed no abnormalities in OUMS-24 cells, while Northern blot analysis demonstrated that the expression of the gene was about one-half that of the normal human fibroblasts. No mutations at the "hot spots" of codons 12 and 61 of H-, K- and N-ras proto-oncogenes were detected in the cells. The cells could grow in soft agar at a cloning efficiency of 6.5%, and upon transplantation into nude mice the cells formed tumors, which were diagnosed as differentiated adenocarcinoma.
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PMID:Establishment and characterization of a human colon cancer cell line, OUMS-23, from a patient with familial adenomatous polyposis. 857 85

The myc gene family has been implicated in multiple cell processes including proliferation, differentiation, tumorigenesis, and apoptosis. For its cellular growth promoting function, Myc must heterodimerize with Max. To study the effect of Myc inactivation on the growth and differentiation properties of epithelial tumor cells, we transfected the H-630 human colon cancer cell line with bm-max, a mutant Max protein in which DNA-binding activity has been abolished. Cells expressing high levels of bm-Max grow poorly, and the morphology of both colonies and single cells is altered. Moreover, increased bm-Max expression results in a prolonged G alpha/G1 phase accompanied by induced expression of p21 (WAF1/CIP1), elevated levels of alkaline phosphatase (ALP) activity, and accumulation of large fat granuli within the cells. These distinctive cell characteristics are associated with differentiation processes in numerous malignant cell lines. The results of this study support a model in which sequestering of endogenous Myc and Max proteins into "basic mutant" dimers lacking DNA-binding activity is sufficient both to inhibit proliferation and to induce changes in cell behavior consistent with differentiation.
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PMID:c-Myc inactivation by mutant Max alters growth and morphology of NCI-H-630 colon cancer cells. 884 36

Bile acids are probably important in colon carcinogenesis. Regional differences in bile acid metabolism within the colon were studied to illuminate the preferential distal occurrence of colon cancer in Western countries. Faeces (24 h) were collected for bile acid measurement from 25 patients with hemicolectomy (nine left and 16 right) and 17 adenoma patients with an intact colon (control subjects). Duodenal bile and cytolytic and alkaline phosphatase activity of faecal water were also studied. The median percentage of deoxycholic acid (DCA) was lower in the hemicolectomy groups [left 48% (range 38-57%), right 45% (2-62%) vs. control subjects 59% (38-70%), P < 0.05]. In duodenal bile, the proportion of DCA in left [4% (1-25%)] was lower than in the patients with right hemicolectomy [19% (0-69%)] and control subjects [24% (7-50%)] P < 0.05. Faecal concentration of protonated DCA was higher in those with right hemicolectomy (0.101 mumol g-1) than in those with left hemicolectomy (0.048 mol g-1), which coincided with a higher cytolytic [right 49% (3-93%), left 2% (1-37%)] and alkaline phosphatase activity [right 6.7 U mL-1 (1.2-40.1 U mL-1), left (2.0 U mL-1 (1-25.7 U mL-1), both P < 0.02]. These findings suggest differences in bile acid metabolism between the proximal and distal colon that may contribute to the disparity in cancer risk.
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PMID:Effects of hemicolectomy on bile acid metabolism in relation to colon carcinogenesis in man. 926 47

The mechanism by which vitamin A prevents or delays chemical carcinogenesis remains unclear. In addition to these antimutagenic and antiproliferative activities, vitamin A seems able to induce programmed cell death. In this study, we assess the suggested role of vitamin A on the in vitro apoptosis induction in a rat colonic tumor cell line. Several concentrations of retinyl palmitate were added in the culture media. We observed cell proliferation by measuring the (3H)thymidine incorporation, cell differentiation by measuring the intestinal alkaline phosphatase expression, and apoptosis induction by DNA fragmentation and morphological evolution of adherent and floating cells. The results show that vitamin A decreases (3H)thymidine incorporation after 1 day of treatment, induces alkaline phosphatase expression, and increases the number of cells falling in apoptosis. This report confirms the role of vitamin A on the induction of cell differentiation, on the inhibition of cell proliferation and shows the vitamin A capacity to induce apoptosis. These results could be attractive to prevent development of colon cancer by vitamin A supplemented diets.
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PMID:Vitamin A and apoptosis in colonic tumor cells. 928 52

Previous studies showed that bile salts had a promoting effect on colon cancer development and this effect was inhibited by ursodeoxycholate (UDC). We recently found that both human colorectal adenomas and carcinomas were associated with a specific decrease in alkaline sphingomyelinase activity. In this work, we compared the effects of ursodeoxycholate and other bile salts on the levels of rat intestinal alkaline sphingomyelinase both in the intestinal loops and after oral administration. Bile salts at different concentrations were injected into intestinal loops and the dissociation of alkaline sphingomyelinase from the mucosa was assayed. We found that bile salts, including taurocholate, taurodeoxycholate, glycocholate, glycochenodeoxycholate, and 3-(3-cholamidopropyl dimethylammonio)-1-propanesulonate (CHAPS), dose dependently dissociated alkaline sphingomyelinase from the intestinal mucosa. UDC alone did not dissociate the enzyme but significantly inhibited the dissociation caused by other bile salts and CHAPS. Feeding rats with 0.3% (w/w) taurocholate for four days decreased peak activity of intestinal alkaline sphingomyelinase by 39% and total activity in the intestine by 20% and increased the output of the enzyme in the feces. In contrast, feeding 0.3% (w/w) UDC for four days increased the peak activity of alkaline sphingomyelinase in the small intestine by 87% and the activity in the colon by 187%. The total activity of alkaline sphingomyelinase was increased by 80% and the output of the enzyme in the feces was only slightly increased by UDC administration. The changes in alkaline phosphatase after feeding taurocholate and UDC were much smaller. Our results indicate that UDC and other bile salts have different effects on the levels of alkaline sphingomyelinase, which may be implicated in their different influences on cancer development reported previously.
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PMID:Effects of ursodeoxycholate and other bile salts on levels of rat intestinal alkaline sphingomyelinase: a potential implication in tumorigenesis. 950 30


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