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)

Addition of transforming growth factor alpha (TGF-alpha) to cultured human keratinocytes results in enhanced expression of TGF-alpha mRNA. This phenomenon of TGF-alpha autoinduction is also observed in a TGF-alpha responsive colon cancer cell line, LIM 1215. In the present study, regulation of TGF-alpha autoinduction is examined in these two cell types. In human keratinocytes, but not in LIM 1215 cells, the increase in steady-state TGF-alpha mRNA following administration of TGF-alpha is due to stabilization of the 4.8-kilobase TGF-alpha transcript, as determined by actinomycin D decay curves. Nuclear run-on experiments confirmed transcriptional control in LIM 1215 cells. Basal and TGF-alpha-stimulated TGF-alpha expression is mediated, at least in part, through a protein kinase C-dependent pathway in both cell types, as determined by the protein kinase C inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H7), which attenuates TGF-alpha mRNA accumulation. In the keratinocytes, but not in the LIM 1215 cells, basal TGF-alpha expression is mediated through an epidermal growth factor receptor-dependent pathway, as determined by antibody blockade of the epidermal growth factor receptor. Thus, differential regulation of TGF-alpha autoinduction exists in these nontransformed and transformed epithelial cell types.
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PMID:Differential regulation of transforming growth factor alpha autoinduction in a nontransformed and transformed epithelial cell. 141 97

The effect of a long-acting somatostatin analogue SMS 201.995 (SMS; Sandoz) on basal and gastrin-stimulated growth of 4 human colon cancer lines was studied in vitro and in vivo. Proliferation assay was done with overnight [75Se]selenomethionine uptake after 5 days of incubation. Gastrin concentrations used were 5e-10 M and 1e-7 M. SMS concentrations were from 2e-12 M to 2e-7 M. Cell lines LIM 1215, LIM 2405, and LIM 2412 were inhibited dose-dependently in both basal and gastrin-stimulated groups. LIM 1863 was slightly stimulated. Based on in vivo growth characteristics, LIM 2412 and LIM 2405 were selected for xenograft study. The dose of 50 micrograms/kg/day was arrived at after a preliminary experiment showed it to be safe and effective. The LIM 2412 xenografts in the SMS-treated animals were 473.3 +/- 99.9 (SD) versus 838.1 +/- 111.3 mm3 in control (P less than 0.05) after 20 days. The LIM 2405 tumors were also significantly inhibited (81.2 +/- 30.0 versus 245.7 +/- 48.3 mm3, P less than 0.01). The effect of SMS appeared to be reversible. Oral SMS at 200 micrograms/kg/day was not absorbed. This study suggests that SMS may have direct antitumor effects in human colon cancer.
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PMID:SMS 201.995 inhibits in vitro and in vivo growth of human colon cancer. 173 55

Immunochemical detection of proteins with antigenic determinants that are dependent on the native spatial conformation of the protein can often pose problems with conventional two-dimensional polyacrylamide gel electrophoresis (2-DE). For example, many antigenic determinants are readily destroyed by reducing agents and/or urea, reagents which are critical components of many of the conventional isoelectric focusing and immobilized-pH-gradient (IPG) protocols used in the first electrophoretic dimension. Here we describe the use of commercially available precast 2-DE gels for performing nonreducing/non-urea 2-DE of proteins extracted from the human colon cancer cell line LIM 1215 with 0.3% Triton X-100 that permit the identification of antigens with conformational determinants by immunoblot analysis. Previous, related studies demonstrated the usefulness of peptide-mass fingerprinting for identifying 2-DE resolved proteins. Here we show how partial protein sequence data obtained by rapid peptide mapping, using capillary column liquid chromatography directly coupled with electrospray ionization tandem mass spectrometric methodologies, enhances the usefulness of this approach for identifying incompletely resolved proteins. The nonreducing 2-DE gel images reported in this study, along with our master 2-DE gel protein database for both normal human colonic crypts and several colon-cancer-derived cell lines, and information regarding microtechniques employed in this laboratory for obtaining structural data on 2-DE resolved proteins can be accessed over the Internet using World Wide Web (URL address: http:@www.ludwig.edu.au).
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PMID:Nonreducing two-dimensional polyacrylamide gel electrophoretic analysis of human colonic proteins. 749 56

Recent evidence suggests a role for sigma (sigma) binding sites in maintenance of cell growth and/or proliferation. The present study examines, for the first time, the effect of sigma binding site ligands on in vitro growth of tumour cells derived from human mammary adenocarcinoma (MCF-7, MDA) and colon carcinoma (LIM 1215, WIDr), and melanoma (Chinnery). Addition of the sigma ligands haloperidol, reduced haloperidol, 1,3-di(2-tolyl)guanidine (DTG), (+)- and (-)-N-allylnormetazocine (SKF 10,047), (+)- and (-)-pentazocine and rimcazole at 6.25, 12.5, 25, 50, 100 microM at the beginning of culture or 24 h later, inhibited cell proliferation in a dose-dependent manner. Light microscopy revealed cell detachment, rounding and cell death. The potency of sigma ligands on melanoma cells was rimcazole > reduced haloperidol > haloperidol = (+)-pentazocine, whereas DTG and (+)- and (-)-SKF 10,047 and (-)-pentazocine had no effect even at 100 microM. In contrast, in MCF-7 cells, rimcazole > reduced haloperidol > haloperidol > (-)-pentazocine > DTG > (+)-pentazocine > (+)-SKF 10,047 > (-)-SKF 10,047. For colon cancer cells, reduced haloperidol > DTG > haloperidol = (-)-pentazocine = (+)-pentazocine = (+)-SKF 10,047. Of all the ligands tested, rimcazole and reduced haloperidol were the most potent inhibitors of cell proliferation. With the exception of one slow-growing colon cancer cell line (LIM 1215), the order of sensitivity of various cell lines to reduced haloperidol, SFK 10,047, DTG, haloperidol and (+)- and (-)-pentazocine was colon carcinoma > mammary adenocarcinoma > melanoma, whereas to rimcazole, the sensitivities of mammary adenocarcinoma and melanoma cells were comparable. The effect of sigma ligands in MCF-7 and melanoma cells was not due to blockade of dopamine D1 and D2 receptors, serotonin (5-HT2) receptors, N-methyl-D-aspartate (NMDA)/phencyclidine receptors, beta-adrenoceptors or opioid receptors, since 100 microM SCH 23390, raclopride, mianserin, (+)-MK-801, propranolol and 1 microM naloxone respectively, were ineffective. However, mianserin and raclopride were inhibitory to melanoma cells and one colon carcinoma cell line, respectively. Taken together, the results are consistent with the recent observation that sigma binding sites may play a role in cell growth and/or cell proliferation.
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PMID:Sigma binding site ligands inhibit cell proliferation in mammary and colon carcinoma cell lines and melanoma cells in culture. 767 99

5-fluorouracil (5-FU) is still the most effective cytotoxic agent for the treatment of human colorectal cancer. Response rates, however, vary between 5-20%. One attempt to improve the effect of 5-FU is through biomodulation. We have previously found the somatostatin analogue, SMS 201.995 (Sandostatin, Sandoz), to inhibit both the in-vitro and in-vivo growth of some human colon cancer cell lines. It may act specifically by means of receptors on the surface of tumour cells, or by reducing the concentration of some growth factors. We report that, when 5-FU at 0.125 and 0.25 micrograms/ml was combined with SMS 201.995 at 10(-12) x 2 to 10(-8) x 2M, an enhanced inhibition of in-vitro growth of two human colorectal cancer cell lines (C170 and LIM 1215) was achieved. Effects were measured using [3H]-thymidine uptake and by a colorimetric assay of cellular respiration (MTT, Promega, Sydney). SMS 201.995 alone has minimal inhibitory effects, whilst 5-FU alone shows inhibition as low as 39.6% of control. When 5-FU was then combined with SMS 201.995, a 10-30% inhibition occurred compared to the 5-FU control. The combination of 5-FU and SMS 201.995 may be a useful method of improving response to human colorectal cancer therapy.
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PMID:SMS 201.995 (Sandostatin) enhances in-vitro effects of 5-fluorouracil in colorectal cancer. 785 48

This study investigated the effect of SMS 201.995 on CEA secretion of human colon cancer cell lines in vitro and as xenografts in nude mice. Using the two cell lines which secreted significant amounts of CEA in the media, there was a 40% and 54% decrease in CEA level at 2e-10M and 2e-9M concentrations of SMS 201.995, respectively, after five days of incubation for LIM 2412 cell line (P < 0.05, both). There was a 13% decrease in CEA at 2e-9M concentration of SMS with the LoVo cell line (P > 0.05). In vivo, there was a direct correlation between the mean volume of the LIM 2412 xenografts and serum CEA level (r = 0.92). When the growth of xenografts was inhibited by SMS, there was a corresponding drop in serum CEA. On the other hand, when tumor sizes remained unchanged, whether after a short duration of SMS treatment or with the oral route, serum CEA was unaffected. Thus, CEA concentration reflected cell number in vitro and tumor size in vivo as a response to treatment with SMS 201.995. The CEA level may therefore be a useful marker during somatostatin treatment to monitor tumor response.
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PMID:Somatostatin inhibits both in-vitro and in-vivo carcinoembryonic antigen secretion by human colon cancer. 849 20

Intestinal trefoil factor (ITF) gene expression was detected in five colon cancer cell lines. ITF was synthesized by mucous cells of LIM 1215 and LIM 1863 lines, from which it is secreted constitutively. The ITF mRNA transcript was estimated to be 0.6 kb. In LIM 1215 cells, the expression of ITF was potently and dose-dependently inhibited by short-chain fatty acids (butyrate > propionate > acetate) within 8 h of application. The inhibitory effect of butyrate was ablated by actinomycin D and preceded its effects on differentiation of LIM 1215 cells as indicated by induction of alkaline phosphatase activity and counting of periodic acid-Schiff-positive cells. The human ITF promoter contained an 11-residue consensus sequence with high homology to the butyrate response element of the cyclin D1 gene. Mobility shift assays show specific binding of this response element to nuclear protein extracts of LIM 1215 cells. We conclude that butyrate inhibits ITF expression in colon cancer cells and that this effect may be mediated transcriptionally and independently of its effects on differentiation.
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PMID:Short-chain fatty acids inhibit intestinal trefoil factor gene expression in colon cancer cells. 965 88

The LIM 1863 colon carcinoma cell line grows as structured organoids around a central lumen, and we have previously demonstrated that the three-dimensional arrangement protects the individual cells from apoptosis induced by an anti-alpha v integrin antibody, 23C6 (Bates et al., 1994). Here we show that the intercellular forces which drive spheroid formation can be overcome by exposure of the cells to a collagen substrate, or more specifically through ligation of the CD44 receptor by a monoclonal antibody. Binding to immobilized anti-CD44 antibody induced a monolayer morphology which is accompanied by fibronectin production and secretion, and expression of the integrin alpha v beta 6. Significantly, the cells of the monolayer acquired resistance to 23C6 antibody-mediated apoptosis over time and this property was sustained even after removal from the monolayer. We provide data to show that this resistance is not dependent on monolayer morphology, constant engagement of the CD44 receptor, loss of the 23C6 antigen, or elevation of Bcl-2 or Bcl-XL protein. The CD44 expressed by LIM 1863 is shown to be the metastatic variant of the molecule therefore these results provide a possible explanation for the selective advantages conferred by expression of this variant for metastasizing colon cancer cells. Overall, the findings of this study support a model for the development of malignancy through the production of specific survival and growth signals as a direct consequence of a signaling event induced by stimulation of an epithelial variant of CD44.
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PMID:Engagement of variant CD44 confers resistance to anti-integrin antibody-mediated apoptosis in a colon carcinoma cell line. 975 19

IGF-II is an autocrine growth factor for many colon cancer cells. This study aimed to determine the role of IGF-II in proliferation and adhesion of LIM 1215 colon cancer cells. RT-PCR demonstrated expression of IGF-I and IGF-II mRNA. Addition of IGF-I or -II increased monolayer proliferation in a dose-dependent manner. Although addition of IGFBP-6 had no effect on basal proliferation, coincubation of IGFBP-6 decreased IGF-II but not IGF-I-induced proliferation. Colony formation in agar was increased by IGF-II, an effect inhibited by coincubation with IGFBP-6. IGFBP-6 alone significantly decreased colony formation. Preincubation of cells with IGF-II increased adhesion to type IV collagen, fibronectin and laminin. IGFBP-6 had no effect on basal cell adhesion but completely inhibited the effects of IGF-II. LIM 1215 colon cancer cells are therefore IGF-responsive but IGF-II is not a major autocrine factor for these cells in monolayer, suggesting heterogeneity between colon carcinoma cell lines with respect to the role of the IGF system.
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PMID:Insulin-like growth factor (IGF)-binding protein-6 inhibits IGF-II-induced but not basal proliferation and adhesion of LIM 1215 colon cancer cells. 1130 78

The conventional approach for analyzing the protein complement of a genome involves the combination of two-dimensional gel electrophoresis (2-DE) and mass spectrometric based protein identification technologies. While 2-DE is a powerful separation technique, it is severely limited by the insolubility of certain classes of proteins (e.g. hydrophobic membrane proteins), as well as the amount of protein that can be processed. Here, we describe a simple procedure for resolving complex mixtures of proteins that involves a combination of free flow electrophoresis (FFE), a liquid-based isoelectric focussing (IEF) method, and sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Resolved proteins were identified by peptide fragment sequencing using capillary column reversed-phase high performance liquid chromatography (RP-HPLC)/mass spectrometry (MS). An initial demonstration of the method was performed using digitonin/ethylenediaminetetraacetic acid EDTA extracted cytosolic proteins from the human colon carcinoma cell line, LIM 1215. Cytosolic proteins were separated by liquid-based IEF (pH range 3-10) into 96 fractions, and each FFE fraction was further fractionated by SDS-PAGE. Selected protein bands were excised from the SDS-PAGE gel, digested in situ with trypsin, and subsequently identified by on-line RP-HPLC/electrospray-ionization ion trap MS. Our results indicate that FFE is: (i) an extremely powerful liquid-based IEF method for resolving proteins; (ii) not limited by the amount of sample that can be loaded onto the instrument; and (iii) capable of fractionating intact protein complexes (a potentially powerful tool for cell-mapping proteomics). An up-to-date list of cytosolic proteins from the human colorectal carcinoma cell line LIM 1215 can be found in the Joint Protein Structure Laboratory (JPSL) proteome database. This information will provide an invaluable resource for future proteomics-based biological studies of colon cancer. The JPSL proteome database can be accessed through the World Wide Web (WWW) network (http://www.ludwig.edu.au/jpsl/jpslhome.html).
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PMID:Continuous free-flow electrophoresis separation of cytosolic proteins from the human colon carcinoma cell line LIM 1215: a non two-dimensional gel electrophoresis-based proteome analysis strategy. 1150 5


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