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

Neurotensin receptor expression was studied in 19 human colon cancer cell lines and normal human colon by i) binding experiments using [125I-Tyr3]-neurotensin; ii) RT-PCR analysis. The following data were obtained: 1) A single class of receptor (Kd ranging from 0.23 to 1.21 nM) was found in 9 out of 19 cell lines but not in normal colonic epithelium; 2) The Bmax was in the range between 1000 and 85 fmoles/mg protein with SW48 > WiDR > Cl 19A > HCT116 > SW480 > SW620 > Cl 16E > Cl 27H > HT-29. No specific binding was measurable in Caco-2, FRI, CBS, EB, HCT-8, 320HRS, 320DM and LS174T cell lines; 3) A single RT-PCR product was observed in HT-29, SW48, WIDR, Cl 19A, SW480, Cl 16E, Cl 27H, SW620 and HCT116, but not in other cell lines or in normal human colon. It is concluded that the expression of neurotensin receptors in human colon cancer cells is regulated at the mRNA level and occurs upon malignancy in > 40% of colon cancer cell lines.
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PMID:Neurotensin receptor and its mRNA are expressed in many human colon cancer cell lines but not in normal colonic epithelium: binding studies and RT-PCR experiments. 752 Nov 65

The intestine is a large endocrine organ, but the dependence of colon cancer on hormones remains unknown. We show here that neurotensin, a paracrine/endocrine peptide in the gut, and the neurotensin receptor antagonist SR 48692 control colon cancer cell growth in vitro and in vivo by interacting with receptors that are ectopically expressed in colon cancers. In cell culture, neurotensin stimulates the growth of human colon cancer cell lines (SW480, SW620, HT29, HCT116 and Cl.19A) expressing the neurotensin receptor NTR1 but does not change the growth of Caco2 cells, which do not express NTR1. In SW480 cells, neurotensin is active in the 10(-10) to 10(-6) M concentration range (ED50 = 0.47 nM) while the neurotensin fragment (I-II) is inactive. Neurotensin also enhances the cellular cloning efficiency of SW480 cells in soft agar by inducing a 50% increase of colony formation. This effect is blocked by SR 48692, which alone does not alter colony formation. Subcutaneous delivery of neurotensin (0.54 micromol/kg every 24 hr) by osmotic pumps to nude mice that have been xenografted with SW480 cells results in a significant increase of tumor volume, i.e., up to 255% of control at day 20 of treatment. SR 48692 administered alone (1.7 micromol/kg every 24 hr) by daily i.p. injections reduces the development of tumors formed by xenografting SW480 cells in nude mice. A significant mean reduction of tumor volume of 38% is observed during the 22-day period of treatment. SR 48692 alone is also active at reducing tumor volume after xenografting HCT116 cells in nude mice. Our results support the notion that colon cancer growth may be dependent on blood-borne neurotensin and suggest that non-peptide neurotensin antagonists, such as SR 48692, may be useful for the development of novel therapeutic strategies of colon cancer.
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PMID:Neurotensin and a non-peptide neurotensin receptor antagonist control human colon cancer cell growth in cell culture and in cells xenografted into nude mice. 993 89

Caspases play a crucial role as apoptotic effectors; their potential implication in tumorigenesis remains to be clarified. We investigated the expression and function of caspases 7, 8, and 9 in colon cancer tissues and cell lines. Immunohistochemistry (IHC) showed downregulation of caspase 7 (22 of 26 cases) and caspase 9 (12 of 26 cases) in colonic cancer samples compared with normal mucosa on the same tissue section. Caspase 8 expression was unchanged or slightly upregulated (19 of 27 cases). The combination of IHC and Western blot analysis showed expression of the proforms of caspases 7, 8, and 9 in HT29-19A and HT29-16E colonic carcinoma cell lines. Apoptosis could be induced by staurosporine in both HT29 cell lines, with a sensitivity similar to that of the HGT cell line, but lower than that of the DAUDI cell line. Apoptosis induction in HT29 cells was concomitant with processing of caspases 3, 7, 8, and 9 and was inhibited by the caspase inhibitor ZVAD. Our data show that (1) human colon cancer cells downregulate caspase 7 and, to a smaller extent, caspase 9 in vivo and (2) in vitro staurosporine-induced apoptosis of colonic cancer cells involves caspases 7 and 9. Caspase 7 deficiency thus appears as a new immunohistochemical marker of colonic neoplasia; its correction represents a potential basis for new therapies.
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PMID:Caspase 7 downregulation as an immunohistochemical marker of colonic carcinoma. 1138 62

The protease-activated receptor-2 (PAR-2) is a G protein-coupled receptor that is cleaved and activated by trypsin. We investigated the expression of PAR-2 and the role of trypsin in cell proliferation in human colon cancer cell lines. A total of 10 cell lines were tested for expression of PAR-2 mRNA by Northern blot and RT-PCR. PAR-2 protein was detected by immunofluorescence. Trypsin and the peptide agonist SLIGKV (AP2) were tested for their ability to induce calcium mobilization and to promote cell proliferation on serum-deprived cells. PAR-2 mRNA was detected by Northern blot analysis in 6 out of 10 cell lines [HT-29, Cl.19A, Caco-2, SW480, HCT-8 and T84]. Other cell lines expressed low levels of transcripts, which were detected only by RT-PCR. Further results were obtained with HT-29 cells: (1) PAR-2 protein is expressed at the cell surface; (2) an increase in intracellular calcium concentration was observed upon trypsin (1-100 nM) or AP2 (10-100 microM) challenges; (3) cells grown in serum-deprived media supplemented with trypsin (0.1-1 nM) or AP2 (1-300 microM) exhibited important mitogenic responses (3-fold increase of cell number). Proliferative effects of trypsin or AP2 were also observed in other cell lines expressing PAR-2. These data show that subnanomolar concentrations of trypsin, acting at PAR-2, promoted the proliferation of human colon cancer cells. The results of this study indicate that trypsin could be considered as a growth factor and unravel a new mechanism whereby serine proteases control colon tumours.
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PMID:Initiation of human colon cancer cell proliferation by trypsin acting at protease-activated receptor-2. 1153 Dec 66

In this work, we showed that human colon cancer cell lines produce trypsin which can activate a receptor for trypsin, the protease-activated receptor-2 (PAR-2), in these cells. RT-PCR experiments showed that trypsinogen transcripts were present in four colon cancer cell lines: T84, Caco-2, HT-29 and C1.19A. By Western blot analysis we found a 25 kDa immunoreactive band identified as trypsinogen I in cell lysates and in the corresponding culture media. Concentrations of trypsin in cell media were found in nanomolar range, thus compatible with activation of protease-activated receptor 2 (PAR-2). This was further demonstrated in a colon cancer cell line (H-29) Ca2+i assay since increases in Ca2+i were observed in response to media from T84, Caco-2 or C1.19A cells that were similar to that observed with 2-5 nM trypsin and were abolished by trypsin inhibitor. Altogether, these data show that colon cancer cell lines produce and secrete trypsin at concentrations compatible with activation of PAR-2. They support possible autocrine/paracrine regulation of PAR-2 activity by trypsin in colon cancer cells.
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PMID:Trypsin is produced by and activates protease-activated receptor-2 in human cancer colon cells: evidence for new autocrine loop. 1188 12

Dietary polyphenols, including anthocyanidins and their glycosides anthocyanins, are suggested to be involved in the protective effects of fruits and vegetables against cancer. Very few data are available concerning the effects of anthocyanidins/anthocyanins on cellular processes induced by growth factors such as neurotensin and epidermal growth factor (EGF), which are implicated in the pathophysiology of colon cancer. Here, we show that neurotensin and EGF caused an increase in the extracellular acidification rate, which could reflect the activity of cellular metabolism, in the human carcinoma cell line HT29 clone 19A. Neurotensin and EGF also caused a strong rise in the intracellular Ca2+ concentration, induced phosphorylation of extracellular signal-regulated kinases (ERK1 and ERK2), and stimulated growth of human carcinoma cells. Cyanidin (10 microM), but not its glycosides cyanin and idaein, was able to inhibit the neurotensin- and EGF-induced increased rate of extracellular acidification. In contrast to N-ethyl-N-isopropyl amiloride, an inhibitor of Na+/H+ exchange, cyanidin did not alter the rate of intracellular pH recovery of cells loaded by NH3/NH4+, indicating that cyanidin inhibits cellular metabolism, rather than directly altering Na+/H+ exchange. Cyanidin, but not cyanin and idaein, was able to inhibit an increase in intracellular Ca2+ concentration induced by neurotensin. Neurotensin- and EGF-induced phosphorylation of ERKs was not affected by cyanidin, cyanin, and idaein at < or = 100 microM. Only cyanidin (100 microM), but not cyanin and idaein, was able to inhibit cellular growth induced by EGF. Thus these findings suggest that a dietary polyphenol cyanidin, but not its glycosides, is a potent inhibitor of mitogen-induced metabolic activity, increase in free intracellular Ca2+, and cellular growth of cultured colon carcinoma cells.
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PMID:Neurotensin-and EGF-induced metabolic activation of colon carcinoma cells is diminished by dietary flavonoid cyanidin but not by its glycosides. 1209 22

Dietary iron may contribute to colon cancer risk via production of reactive oxygen species (ROS). The aim of the study was to determine whether physiological ferric/ferrous iron induces oxidative DNA damage in human colon cells. Therefore, differentiated human colon tumour cells (HT29 clone 19A) were incubated with ferric-nitrilotriacetate (Fe-NTA) or with haemoglobin and DNA breaks and oxidised bases were determined by microgelelectrophoresis. The effects of Fe-NTA were measured with additional H(2)O(2) (75microM) and quercetin (25-100microM) treatment. Analytic detection of iron in cell cultures, treated with 250microM Fe-NTA for 15 min to 24h, showed that 48.02+/-5.14 to 68.31+/-2.11% were rapidly absorbed and then detectable in the cellular fraction. Fe-NTA (250-1000microM) induced DNA breaks and oxidised bases, which were enhanced by subsequent H(2)O(2) exposure. Simultaneous incubation of HT29 clone 19A cells with Fe-NTA and H(2)O(2) for 15 min, 37 degrees C did not change the effect of H(2)O(2) alone. The impact of Fe-NTA and H(2)O(2)-induced oxidative damage is reduced by the antioxidant quercetin (75-67% of H(2)O(2)-control). Haemoglobin was as effective as Fe-NTA in inducing DNA damage. From these results we can conclude that iron is taken up by human colon cells and participates in the induction of oxidative DNA damage. Thus, iron or its capacity to catalyse ROS-formation, is an important colon cancer risk factor. Inhibition of damage by quercetin reflects the potential of antioxidative compounds to influence this risk factor. Quantitative data on the genotoxic impact of ferrous iron (e.g. from red meat) relative to the concentrations of antioxidants (from plant foods) in the gut are now needed to determine the optimal balance of food intake that will reduce exposure to this type of colon cancer risk factor.
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PMID:Iron-overload induces oxidative DNA damage in the human colon carcinoma cell line HT29 clone 19A. 1216 Sep

A new intestinal antiproliferative factor (IAF) with an approximate molecular weight of 120 kDa has been purified from the human small intestine. This factor blocks the progression of human colon adenocarcinoma cells HT-29 from the G1 to the S phase. IAF, specific of the lower part of the digestive tract, was detected rather late in mouse embryonic development. For determination of the specific intestinal cell producing IAF, long-term differentiated mucus-secreting HT-29 Cl 16E and enterocytic HT-29 Cl 19A cell lines were used. IAF is synthesized exclusively in the intestinal goblet cells; it is processed in the RER and Golgi complex before being excreted in secretory vesicles independently of mucin secretion. IAF can be considered a growth inhibitor of intestinal proliferation for the same reason as TGF-beta. However, two features differentiate it from TGF-beta: (1) the intestinal cell type synthesizing it, and (2) the delay in its expression in embryonic development. Particular interest was paid to IAF expression in pathological conditions using human colon biopsies. IAF was consistently recovered in biopsies from patients with inflammatory bowel diseases and benign tumors, but it was never detected in malignant tumors. IAF could represent a marker of colon cancer owing to its absence from malignant tumors.
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PMID:Immunolocalization of a new intestinal antiproliferative factor in human intestinal epithelial cells. 1245 77