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.

scholarly journals Upregulated Na+/H+-Exchange Protects Human Colon Cancer Tissue against Intracellular Acidification

2019 ◽  
Vol 2019 ◽  
pp. 1-5 ◽  
Author(s):  
Ninna C. S. Voss ◽  
Henrik Kold-Petersen ◽  
Mikkel B. Henningsen ◽  
Casper Homilius ◽  
Ebbe Boedtkjer
Keyword(s):  
Colon Cancer ◽  
Steady State ◽  
Intracellular Ph ◽  
Human Colon ◽  
Cancer Tissue ◽  
Normal Colon ◽  
Colon Tissue ◽  
Colon Cancer Tissue ◽  
Human Colon Cancer ◽  
Acid Extrusion

Increased metabolism accelerates local acid production in cancer tissue. The mechanisms eliminating acidic waste products from human colon cancer tissue represent promising therapeutic targets for pharmacological manipulation in order to improve prognosis for the increasing number of patients with colon cancer. We sampled biopsies of human colonic adenocarcinomas and matched normal colon tissue from patients undergoing colon cancer surgery. We measured steady-state intracellular pH and rates of net acid extrusion in freshly isolated human colonic crypts based on fluorescence microscopy. Net acid extrusion was almost entirely (>95%) Na+-dependent. The capacity for net acid extrusion was increased and steady-state intracellular pH elevated around 0.5 in crypts from colon cancer tissue compared with normal colon tissue irrespective of whether they were investigated in the presence or absence of CO2/HCO3–. The accelerated net acid extrusion from the human colon cancer tissue was sensitive to the Na+/H+-exchange inhibitor cariporide. We conclude that enhanced net acid extrusion via Na+/H+-exchange elevates intracellular pH in human colon cancer tissue.

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

scholarly journals Enhanced nitric oxide signaling amplifies vasorelaxation of human colon cancer feed arteries

2019 ◽  
Vol 316 (1) ◽  
pp. H245-H254 ◽  
Author(s):  
Ninna C. S. Voss ◽  
Henrik Kold-Petersen ◽  
Ebbe Boedtkjer
Keyword(s):  
Nitric Oxide ◽  
Colon Cancer ◽  
Human Colon ◽  
No Synthase ◽  
Cancer Tissue ◽  
Solid Cancer ◽  
Tumor Perfusion ◽  
Normal Colon ◽  
Human Colon Cancer ◽  
Feed Arteries

Inadequate perfusion of solid cancer tissue results in low local nutrient and oxygen levels and accumulation of acidic waste products. Previous investigations have focused primarily on tumor blood vessel architecture, and we lack information concerning functional differences between arteries that deliver blood to solid cancer tissue versus normal tissue. Here, we use isometric myography to study resistance-sized arteries from human primary colon adenocarcinomas and matched normal colon tissue. Vasocontraction of colon cancer feed arteries in response to endothelin-1 and thromboxane stimulation is attenuated compared with normal colon arteries despite similar wall dimensions and comparable contractions to arginine vasopressin and K+-induced depolarization. Acetylcholine-induced vasorelaxation and endothelial NO synthase expression are increased in colon cancer feed arteries compared with normal colon arteries, whereas vasorelaxation to exogenous NO donors is unaffected. In congruence, the differences in vasorelaxant and vasocontractile function between colon cancer feed arteries and normal colon arteries decrease after NO synthase inhibition. Rhythmic oscillations in vascular tone, known as vasomotion, are of lower amplitude but similar frequency in colon cancer feed arteries compared with normal colon arteries. In conclusion, higher NO synthase expression and elevated NO signaling amplify vasorelaxation and attenuate vasocontraction of human colon cancer feed arteries. We propose that enhanced endothelial function augments tumor perfusion and represents a potential therapeutic target. NEW & NOTEWORTHY Local vascular resistance influences tumor perfusion. Arteries supplying human colonic adenocarcinomas show enhanced vasorelaxation and reduced vasocontraction mainly due to elevated nitric oxide-mediated signaling. Rhythmic oscillations in tone, known as vasomotion, are attenuated in colon cancer feed arteries.

Expression of Gelatinase-A (MMP-2) in Human Colon Cancer and Normal Colon Mucosa

Tumor Biology ◽  
2001 ◽  
Vol 22 (6) ◽  
pp. 383-389 ◽  
Author(s):  
S. Papadopoulou ◽  
A. Scorilas ◽  
N. Arnogianaki ◽  
B. Papapanayiotou ◽  
A. Tzimogiani ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Human Colon ◽  
Gelatinase A ◽  
Colon Mucosa ◽  
Normal Colon ◽  
Human Colon Cancer ◽  
Normal Colon Mucosa

scholarly journals Enhanced 4-Hydroxynonenal Resistance inKEAP1Silenced Human Colon Cancer Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-16 ◽  
Author(s):  
Kyeong-Ah Jung ◽  
Mi-Kyoung Kwak
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Target Gene ◽  
Human Colon ◽  
Adduct Formation ◽  
Mrna Levels ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Ht29 Cells ◽  
Human Colon Cancer Cells

Nuclear factor erythroid 2-related factor 2 (NRF2) is the transcription factor that regulates an array of antioxidant/detoxifying genes for cellular defense. The conformational changes of Kelch-like ECH-associated protein 1 (KEAP1), a cytosolic repressor protein of NRF2, by various stimuli result in NRF2 liberation and accumulation in the nucleus. In the present study, we aimed to investigate the effect ofKEAP1knockdown on NRF2 target gene expression and its toxicological implication using human colon cancer cells. The stableKEAP1-knockdown HT29 cells exhibit elevated levels of NRF2 and its target gene expressions. In particular, the mRNA levels of aldo-keto reductases (AKR1C1, 1C2, 1C3, 1B1, and 1B10) were substantially increased inKEAP1silenced HT29 cells. These differential AKRs expressions appear to contribute to protection against oxidative stress. TheKEAP1-knockdown cells were relatively more resistant to hydrogen peroxide (H2O2) and 4-hydroxynonenal (4HNE) compared to the control cells. Accordantly, we observed accumulation of 4HNE protein adducts in H2O2- or 4HNE-treated control cells, whereasKEAP1-knockdown cells did not increase adduct formation. The treatment ofKEAP1-silenced cells with AKR1C inhibitor flufenamic acid increased 4HNE-induced cellular toxicity and protein adduct formation. Taken together, these results indicate that AKRs, which are NRF2-dependent highly inducible gene clusters, play a role in NRF2-mediated cytoprotection against lipid peroxide toxicity.

scholarly journals cis-Golgi resident proteins and O-glycans are abnormally compartmentalized in the RER of colon cancer cells

1993 ◽  
Vol 105 (3) ◽  
pp. 819-830 ◽  
Author(s):  
G. Egea ◽  
C. Franci ◽  
G. Gambus ◽  
T. Lesuffleur ◽  
A. Zweibaum ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Golgi Apparatus ◽  
Cancer Cells ◽  
Neoplastic Transformation ◽  
Human Colon ◽  
Colon Cancer Cells ◽  
Normal Colon ◽  
Human Colon Cancer ◽  
Protein Disulphide Isomerase ◽  
Cancer Tissues

Neoplastic transformation is commonly associated with altered glycosylation of proteins and lipids. To understand the basis for altered mucin glycosylation, we have examined the distribution of RER markers, a cis-Golgi resident protein, and the GalNAc alpha-O-Ser/Thr epitope (Tn) in human colon cancer cells and in normal colon. In cultured mucin-producing colon cancer cells, Gal-NAc alpha-O-Ser/Thr was found in mucin droplets and in RER cisternae. In addition, the Golgi apparatus was disorganized in a proportion of cells and a 130 kDa cis-Golgi resident protein was also abnormally redistributed to the RER. The distribution of the MUC2 intestinal apomucin, protein disulphide isomerase, Gal-NAc alpha-O-Ser/Thr, and the 130 kDa cis-Golgi resident protein was analysed in normal colon and in colon cancer tissues. In normal colon, MUC2 apomucin and protein disulphide isomerase were located in the RER, whereas the cis-Golgi resident protein and GalNAc alpha-O-Ser/Thr were detected only in the cis-Golgi compartment. In contrast, the two Golgi markers colocalized with the MUC2 apomucin and protein disulphide isomerase in the RER of colon cancer cells. On the basis of these results, we propose that in colon cancer cells a redistribution of molecules normally present in the Golgi apparatus takes place; this alteration may contribute to the abnormal glycosylation of proteins and lipids associated with neoplastic transformation.

scholarly journals CHK Methylation Is Elevated in Colon Cancer Cells and Contributes to the Oncogenic Properties

2021 ◽  
Vol 9 ◽  
Author(s):  
Shudong Zhu ◽  
Yan Zhu ◽  
Qiuwen Wang ◽  
Yi Zhang ◽  
Xialing Guo
Keyword(s):  
Dna Methylation ◽  
Colon Cancer ◽  
Cancer Cells ◽  
Human Colon ◽  
Dna Methyltransferases ◽  
Colon Cancer Cells ◽  
Normal Colon ◽  
Human Colon Cancer ◽  
Colon Cells ◽  
Matrigel Invasion

Src is an important oncogene that plays key roles in multiple signal transduction pathways. Csk-homologous kinase (CHK) is a kinase whose molecular roles are largely uncharacterized. We previously reported expression of CHK in normal human colon cells, and decreased levels of CHK protein in colon cancer cells leads to the activation of Src (Zhu et al., 2008). However, how CHK protein expression is downregulated in colon cancer cells has been unknown. We report herein that CHK mRNA was decreased in colon cancer cells as compared to normal colon cells, and similarly in human tissues of normal colon and colon cancer. Increased levels of DNA methylation at promotor CpG islands of CHK gene were observed in colon cancer cells and human colon cancer tissues as compared to their normal healthy counterparts. Increased levels of DNA methyltransferases (DNMTs) were also observed in colon cancer cells and tissues. DNA methylation and decreased expression of CHK mRNA were inhibited by DNMT inhibitor 5-Aza-CdR. Cell proliferation, colony growth, wound healing, and Matrigel invasion were all decreased in the presence of 5-Aza-CdR. These results suggest that increased levels of DNA methylation, possibly induced by enhanced levels of DNMT, leads to decreased expression of CHK mRNA and CHK protein, promoting increased oncogenic properties in colon cancer cells.

scholarly journals Gossypol decreased cell viability and down-regulated the expression of a number of genes in human colon cancer cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Heping Cao ◽  
Kandan Sethumadhavan ◽  
Fangping Cao ◽  
Thomas T. Y. Wang
Keyword(s):  
Colon Cancer ◽  
Cell Viability ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Human Colon ◽  
Mrna Levels ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Number Of Genes ◽  
Human Colon Cancer Cells

AbstractPlant polyphenol gossypol has anticancer activities. This may increase cottonseed value by using gossypol as a health intervention agent. It is necessary to understand its molecular mechanisms before human consumption. The aim was to uncover the effects of gossypol on cell viability and gene expression in cancer cells. In this study, human colon cancer cells (COLO 225) were treated with gossypol. MTT assay showed significant inhibitory effect under high concentration and longtime treatment. We analyzed the expression of 55 genes at the mRNA level in the cells; many of them are regulated by gossypol or ZFP36/TTP in cancer cells. BCL2 mRNA was the most stable among the 55 mRNAs analyzed in human colon cancer cells. GAPDH and RPL32 mRNAs were not good qPCR references for the colon cancer cells. Gossypol decreased the mRNA levels of DGAT, GLUT, TTP, IL families and a number of previously reported genes. In particular, gossypol suppressed the expression of genes coding for CLAUDIN1, ELK1, FAS, GAPDH, IL2, IL8 and ZFAND5 mRNAs, but enhanced the expression of the gene coding for GLUT3 mRNA. The results showed that gossypol inhibited cell survival with decreased expression of a number of genes in the colon cancer cells.

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