Variation in cytosolic protein expression between human colon tumors that differ with regard to differentiation class.

1988 ◽  
Vol 34 (1) ◽  
pp. 71-75 ◽  
Author(s):  
T J Nalty ◽  
C W Taylor ◽  
L C Yeoman
Keyword(s):  
Human Colon ◽  
Human Colon Cancer ◽  
Two Dimensional Gel Electrophoresis ◽  
Colon Tumors ◽  
Marker Proteins ◽  
Isoelectric Points ◽  
Molecular Masses ◽  
Poorly Differentiated ◽  
Differentiation Marker ◽  
Individual Differentiation

Abstract Using a combination of two-dimensional gel electrophoresis, silver staining, and a 16-quadrant grid system, we established a set of composite patterns for the colon tumor cytosol proteins of well, moderately, and poorly differentiated tumors. These composite patterns were found to be characteristic of the three individual differentiation classes for colon tumors. The apparent relative molecular masses (Mr) of the resolved proteins ranged from 14,000 to 105,000 and their isoelectric points from pH 5.2 to 8.4. Although the vast majority of the proteins identified in the composite patterns were common, a comparison based upon these patterns revealed two qualitative and seven quantitative protein differences. The qualitative differences were identified by apparent Mr X 10(-3)/pI coordinates of 73/7.2 and 66/6.2. Quantitative differences were identified by Mr X 10(-3)/pI coordinates of 71/6.0, 59/6.7, 57/6.7, 56/5.4, 52/6.1, 30/5.8, and 18/6.2. These cytosolic differentiation marker proteins may facilitate the diagnosis, staging, and monitoring of human colon cancer.

Expression of G-protein alpha subunits in normal rat colonocytes, azoxymethane (AOM)-induced colon tumors, and human colon cancer-derived cell lines

1995 ◽  
Vol 108 (4) ◽  
pp. A954 ◽  
Author(s):  
M.J.G. Bolt ◽  
R.J. Mailloux ◽  
R. Wali ◽  
B. Frawley ◽  
B. Scaglione-Sewell ◽  
...  
Keyword(s):  
Colon Cancer ◽  
G Protein ◽  
Cell Lines ◽  
Human Colon ◽  
Human Colon Cancer ◽  
Colon Tumors ◽  
Alpha Subunits ◽  
Normal Rat

BNIP3L (Nix) expression in colon cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15097-e15097
Author(s):  
J. E. Littlejohn ◽  
D. Jupiter ◽  
X. Cao ◽  
L. Zhang ◽  
M. Shabahang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Human Colon ◽  
Mrna Levels ◽  
Normal Colon ◽  
Colon Tissue ◽  
Human Colon Cancer ◽  
Variable Expression ◽  
Colon Tumors ◽  
Normal Colon Tissue ◽  
Protein Levels

e15097 Background: Microenvironmental adaptation to hypoxic conditions is critical for a cell to survive in a growing solid tumor. BNIP3L (Nix) mediates apoptosis during hypoxia in cancer cell lines, and Nix knockdown promotes tumor growth in-vivo through decreased apoptosis and increased proliferation, suggesting a means by which cells can adapt. Little is known specifically about Nix expression and its importance in human colon cancer. To gain insight into expression of this gene in colon tumors, the present study analyzed mRNA microarray data from 227 colon tumors and 22 normal colon tissue samples and queried differential expression of Nix. These results were compared to the protein levels present in human colon tumors. Methods: mRNA expression of 227 human colon tumors (made available by the Expression Project for Oncology (expO)) and 22 normal colon samples (retrieved from the Gene Expression Omnibus (GEO)) was analyzed. These samples were hybridized to the Affymetrix GeneChip Human Genome U133 Plus 2.0 Array, assaying 17,726 NCBI Entrez genes. Immunohistochemistry was performed on human tissue microarray CO701 (US Biomax, Inc.) containing 62 tumor samples. Results: Nix mRNA levels were shown to increase from normal to cancer (log-fold change of 0.961, Benjamini-Hochberg FDR adjusted p < 0.001). IHC demonstrated variable levels of Nix present in colon tumors: 38/62 (61.3%) of tumors stained positive for Nix while 24/62 (38.7%) were negative. Conclusions: We have shown that mRNA levels of Nix are upregulated in the transition from normal colon tissue to cancer but that protein levels in tumors demonstrate variable expression. This suggests that silencing of Nix occurs at various stages of tumorigenic progression and results in isolated populations of cells within a growing tumor that are uniquely resistant to apoptosis. Better understanding of Nix in the context of a growing colon tumor is needed and could lead to development of more successful therapeutics. No significant financial relationships to disclose.

Differential expression proteomics of human colon cancer

2006 ◽  
Vol 290 (6) ◽  
pp. G1329-G1338 ◽  
Author(s):  
Roberto Mazzanti ◽  
Michela Solazzo ◽  
Ornella Fantappié ◽  
Sarah Elfering ◽  
Pietro Pantaleo ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Human Colon ◽  
Intestinal Wall ◽  
Differentially Expressed ◽  
Colon Tissue ◽  
Human Colon Cancer ◽  
Two Dimensional Gel Electrophoresis ◽  
Apoptosis Pathway ◽  
Early Stages ◽  
Proteomic Approach

The focus of this study was to use differential protein expression to investigate operative pathways in early stages of human colon cancer. Colorectal cancer represents an ideal model system to study the development and progression of human tumors, and the proteomic approach avoids overlooking posttranslational modifications not detected by microarray analyses and the limited correlation between transcript and protein levels. Colon cancer samples, confined to the intestinal wall, were analyzed by expression proteomics and compared with matched samples from normal colon tissue. Samples were processed by two-dimensional gel electrophoresis, and spots differentially expressed and consistent across all patients were identified by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry analyses and by Western blot analyses. After differentially expressed proteins and their metabolic pathways were analyzed, the following main conclusions were achieved for tumor tissue: 1) a shift from β-oxidation, as the main source of energy, to anaerobic glycolysis was observed owed to the alteration of nuclear- versus mitochondrial-encoded proteins and other proteins related to fatty acid and carbohydrate metabolism; 2) lower capacity for Na+and K+cycling; and 3) operativity of the apoptosis pathway, especially the mitochondrial one. This study of the human colon cancer proteome represents a step toward a better understanding of the metabolomics of colon cancer at early stages confined to the intestinal wall.

scholarly journals Pharmacological inhibition of Mdm2 triggers growth arrest and promotes DNA breakage in mouse colon tumors and human colon cancer cells

2011 ◽  
Vol 51 (5) ◽  
pp. 363-378 ◽  
Author(s):  
Marc J. Rigatti ◽  
Rajeev Verma ◽  
Glenn S. Belinsky ◽  
Daniel W. Rosenberg ◽  
Charles Giardina
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Growth Arrest ◽  
Human Colon ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Dna Breakage ◽  
Colon Tumors ◽  
Mouse Colon ◽  
Human Colon Cancer Cells

scholarly journals Inactivation of Adenomatous Polyposis Coli Reduces Bile Acid/Farnesoid X Receptor Expression through Fxr gene CpG Methylation in Mouse Colon Tumors and Human Colon Cancer Cells

2015 ◽  
Vol 146 (2) ◽  
pp. 236-242 ◽  
Author(s):  
Ornella I Selmin ◽  
Changming Fang ◽  
Adam M Lyon ◽  
Tom C Doetschman ◽  
Patricia A Thompson ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Bile Acid ◽  
Colonic Mucosa ◽  
Human Colon ◽  
Cpg Methylation ◽  
Farnesoid X Receptor ◽  
Human Colon Cancer ◽  
Colon Tumors ◽  
Hct 116 ◽  
Cox 2

Abstract Background: The farnesoid X receptor (FXR) regulates bile acid (BA) metabolism and possesses tumor suppressor functions. FXR expression is reduced in colorectal tumors of subjects carrying inactivated adenomatous polyposis coli (APC). Identifying the mechanisms responsible for this reduction may offer new molecular targets for colon cancer prevention. Objective: We investigated how APC inactivation influences the regulation of FXR expression in colonic mucosal cells. We hypothesized that APC inactivation would epigenetically repress nuclear receptor subfamily 1, group H, member 4 (FXR gene name) expression through increased CpG methylation. Methods: Normal proximal colonic mucosa and normal-appearing adjacent colonic mucosa and colon tumors were collected from wild-type C57BL/6J and Apc-deficient (ApcMin/+) male mice, respectively. The expression of Fxr, ileal bile acid-binding protein (Ibabp), small heterodimer partner (Shp), and cyclooxygenase-2 (Cox-2) were determined by real-time polymerase chain reaction. In both normal and adjacent colonic mucosa and colon tumors, we measured CpG methylation of Fxr in bisulfonated genomic DNA. In vitro, we measured the impact of APC inactivation and deoxycholic acid (DCA) treatment on FXR expression in human colon cancer HCT-116 cells transfected with silencing RNA for APC and HT-29 cells carrying inactivated APC. Results: In ApcMin/+ mice, constitutive CpG methylation of the Fxrα3/4 promoter was linked to reduced (60–90%) baseline Fxr, Ibabp, and Shp and increased Cox-2 expression in apparently normal adjacent mucosa and colon tumors. Apc knockdown in HCT-116 cells increased cellular myelocytomatosis (c-MYC) and lowered (∼50%) FXR expression, which was further reduced (∼80%) by DCA. In human HCT-116 but not HT-29 colon cancer cells, DCA induced FXR expression and lowered CpG methylation of FXR. Conclusions: We conclude that the loss of APC function favors the silencing of FXR expression through CpG hypermethylation in mouse colonic mucosa and human colon cells, leading to reduced expression of downstream targets (SHP, IBABP) involved in BA homeostasis while increasing the expression of factors (COX-2, c-MYC) that contribute to inflammation and colon cancer.

Identification of proteins potentially involved in proximal–distal pattern formation in the regenerating forelimb of the newt

1992 ◽  
Vol 70 (5) ◽  
pp. 285-290 ◽  
Author(s):  
Robert L. Carlone ◽  
Robert P. Boulianne ◽  
Andrew J. Link
Keyword(s):  
Retinoic Acid ◽  
Pattern Formation ◽  
Positional Information ◽  
Gene Products ◽  
Two Dimensional Gel Electrophoresis ◽  
Regeneration Stage ◽  
Isoelectric Points ◽  
Specific Proteins ◽  
Molecular Masses ◽  
Regeneration Blastema

We have used high resolution two-dimensional gel electrophoresis to identify and characterize proteins that may represent products of genes involved in establishing positional information along the proximal–distal axis of the regenerating forelimb of the newt Notophthalmus viridescens. At least 24 proteins have been found whose synthesis and (or) abundance is increased in proximal (midstylopodial) regenerates relative to midzeugopodial (distal) regenerates at either of two regeneration stages, the early dedifferentiation and moderate bud stages. Four of these same proteins show an axial asymmetry at both stages. Ten distal-specific proteins were also identified, although only one was common to both stages. More significantly, 6 of these 34 proteins (molecular masses of 73, 73, 51.5, 44.0, 19.5, and 16.5 kilodaltons and isoelectric points of 6.70, 6.74, 6.0, 6.05, 5.9, and 6.98, respectively) are regulated to proximal levels by treatment of distal regenerates with retinoic acid (RA) at both stages. An additional five are proximalized by RA at only one regeneration stage. Since the effect of RA is to proximalize positional information in blastema cells, these 11 proteins represent gene products that could be involved in a biochemical cascade leading to the establishment of positional information in the regenerating limb along this axis.Key words: positional information, retinoic acid, regeneration, blastema, pattern formation, newt.

scholarly journals A novel mouse model of sporadic colon cancer induced by combination of conditional Apc genes and chemical carcinogen in the absence of Cre recombinase

2019 ◽  
Vol 40 (11) ◽  
pp. 1376-1386 ◽  
Author(s):  
Jeffrey S Souris ◽  
Hannah J Zhang ◽  
Urszula Dougherty ◽  
Nai-Tzu Chen ◽  
Joseph V Waller ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Small Intestine ◽  
Mouse Model ◽  
Mouse Models ◽  
Cancer Biology ◽  
Human Colon ◽  
Cre Recombinase ◽  
Tumor Incidence ◽  
Human Colon Cancer ◽  
Colon Tumors

AbstractAlthough valuable insights into colon cancer biology have been garnered from human colon cancer cell lines and primary colonic tissues, and animal studies using human colon cancer xenografts, immunocompetent mouse models of spontaneous or chemically induced colon cancer better phenocopy human disease. As most sporadic human colon tumors present adenomatous polyposis coli (APC) gene mutations, considerable effort has gone into developing mice that express mutant Apc alleles that mimic human colon cancer pathogenesis. A serious limitation of many of these Apc-mutant murine models, however, is that these mice develop numerous tumors in the small intestine but few, if any, in the colon. In this work, we examined three spontaneous mouse models of colon tumorigenesis based upon the widely used multiple intestinal neoplasia (Min) mouse: mice with either constitutive or conditional Apc mutations alone or in combination with caudal-related homeobox transcription factor CDX2P-Cre transgene — either with or without exposure to the potent colon carcinogen azoxymethane. Using the CDX2 promoter to drive Cre recombinase transgene expression effectively inactivated Apc in colonocytes, creating a model with earlier tumor onset and increased tumor incidence/burden, but without the Min mouse model’s small intestine tumorigenesis and susceptibility to intestinal perforation/ulceration/hemorrhage. Most significantly, azoxymethane-treated mice with conditional Apc expression, but absent the Cre recombinase gene, demonstrated nearly 50% tumor incidence with two or more large colon tumors per mouse of human-like histology, but no small intestine tumors — unlike the azoxymethane-resistant C57BL/6J-background Min mouse model. As such this model provides a robust platform for chemoprevention studies.

Leptin is a growth factor for human colon cancer cells

2001 ◽  
Vol 120 (5) ◽  
pp. A493-A493
Author(s):  
J HARDWICK ◽  
G VANDENBRINK ◽  
S VANDEVENTER ◽  
M PEPPELENBOSCH
Keyword(s):  
Colon Cancer ◽  
Growth Factor ◽  
Cancer Cells ◽  
Human Colon ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Human Colon Cancer Cells
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