Gene Expression Profile of Colon Cancer Cell Lines Treated with SN38

Colorectal cancers (CRCs) account for nearly 10% of all cancer deaths in industrialized countries. Recent evidence points to a central role for the nuclear receptor liver receptor homolog-1 (LRH-1) in intestinal tumorigenesis. Interaction of LRH-1 with the Wnt/β-catenin pathway, highly active in a critical subpopulation of CRC cells, underscores the importance of elucidating LRH-1’s role in this disease. Reduction of LRH-1 diminishes tumor burden in murine models of CRC; however, it is not known whether LRH-1 is required for tumorigenesis, for proliferation, or for both. In this work, we address this question through shRNA-mediated silencing of LRH-1 in established CRC cell lines. LRH-1 mRNA knockdown results in significantly impaired proliferation in a cell line highly expressing the receptor and more modest impairment in a cell line with moderate LRH-1 expression. Cell-cycle analysis shows prolongation of G0/G1 with LRH-1 silencing, consistent with LRH-1 cell-cycle influences in other tissues. Cluster analysis of microarray gene expression demonstrates significant genome wide alterations with major effects in cell-cycle regulation, signal transduction, bile acid and cholesterol metabolism, and control of apoptosis. This study demonstrates a critical proproliferative role for LRH-1 in established colon cancer cell lines. LRH-1 exerts its effects via multiple signaling networks. Our results suggest that selected CRC patients could benefit from LRH-1 inhibitors.

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ADAMTS1, CRABP1, and NR3C1 Identified as Epigenetically Deregulated Genes in Colorectal Tumorigenesis

Analytical Cellular Pathology ◽

10.1155/2006/949506 ◽

2006 ◽

Vol 28 (5-6) ◽

pp. 259-272 ◽

Cited By ~ 3

Author(s):

Guro E. Lind ◽

Kristine Kleivi ◽

Gunn I. Meling ◽

Manuel R. Teixeira ◽

Espen Thiis-Evensen ◽

...

Keyword(s):

Gene Expression ◽

Colon Cancer ◽

Cell Lines ◽

Cancer Cell ◽

Cpg Island ◽

Promoter Hypermethylation ◽

Cancer Cell Lines ◽

Colon Cancer Cell ◽

Colorectal Carcinomas ◽

Colon Cancer Cell Lines

Background: Gene silencing through CpG island hypermethylation is a major mechanism in cancer development. In the present study, we aimed to identify and validate novel target genes inactivated through promoter hypermethylation in colorectal tumor development. Methods: With the use of microarrays, the gene expression profiles of colon cancer cell lines before and after treatment with the demethylating agent 5-aza-2′-deoxycytidine were identified and compared. The expression of the responding genes was compared with microarray expression data of primary colorectal carcinomas. Four of these down-regulated genes were subjected to methylation-specific PCR, bisulphite sequencing, and quantitative gene expression analysis using tumors (n=198), normal tissues (n=44), and cell lines (n=30). Results: Twenty-one genes with a CpG island in their promoter responded to treatment in cell lines, and were simultaneously down-regulated in primary colorectal carcinomas. Among 20 colon cancer cell lines, hypermethylation was subsequently identified for three of four analyzed genes, ADAMTS1 (85%), CRABP1 (90%), and NR3C1 (35%). For the latter two genes, hypermethylation was significantly associated with absence or reduced gene expression. The methylation status of ADAMTS1, CRABP1, and NR3C1 was further investigated in 116 colorectal carcinomas and adenomas. Twenty-three of 63 (37%), 7/60 (12%), and 2/63 (3%) adenomas, as well as 37/52 (71%), 25/51 (49%), and 13/51 (25%) carcinomas were hypermethylated for the respective genes. These genes were unmethylated in tumors (n=82) from three other organs, prostate, testis, and kidney. Finally, analysis of normal colorectal mucosa demonstrated that the observed promoter hypermethylation was cancer-specific. Conclusion: By using a refined microarray screening approach we present three genes with cancer-specific hypermethylation in colorectal tumors, ADAMTS1, CRABP1, and NR3C1.

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Analysis of Cross-Association between mRNA Expression and RNAi Efficacy for Predictive Target Discovery in Colon Cancers

Cancers ◽

10.3390/cancers12113091 ◽

2020 ◽

Vol 12 (11) ◽

pp. 3091

Author(s):

Euna Jeong ◽

Yejin Lee ◽

Youngju Kim ◽

Jieun Lee ◽

Sukjoon Yoon

Keyword(s):

Gene Expression ◽

Colon Cancer ◽

Mrna Expression ◽

Cell Lines ◽

Cancer Cell ◽

Large Scale ◽

Cancer Cell Lines ◽

Colon Cancer Cell ◽

Transcriptional Networks ◽

Colon Cancer Cell Lines

The availability of large-scale, collateral mRNA expression and RNAi data from diverse cancer cell types provides useful resources for the discovery of anticancer targets for which inhibitory efficacy can be predicted from gene expression. Here, we calculated bidirectional cross-association scores (predictivity and descriptivity) for each of approximately 18,000 genes identified from mRNA and RNAi (i.e., shRNA and sgRNA) data from colon cancer cell lines. The predictivity score measures the difference in RNAi efficacy between cell lines with high vs. low expression of the target gene, while the descriptivity score measures the differential mRNA expression between groups of cell lines exhibiting high vs. low RNAi efficacy. The mRNA expression of 90 and 74 genes showed significant (p < 0.01) cross-association scores with the shRNA and sgRNA data, respectively. The genes were found to be from diverse molecular classes and have different functions. Cross-association scores for the mRNA expression of six genes (CHAF1B, HNF1B, HTATSF1, IRS2, POLR2B and SATB2) with both shRNA and sgRNA efficacy were significant. These genes were interconnected in cancer-related transcriptional networks. Additional experimental validation confirmed that siHNF1B efficacy is correlated with HNF1B mRNA expression levels in diverse colon cancer cell lines. Furthermore, KIF26A and ZIC2 gene expression, with which shRNA efficacy displayed significant scores, were found to correlate with the survival rate from colon cancer patient data. This study demonstrates that bidirectional predictivity and descriptivity calculations between mRNA and RNAi data serve as useful resources for the discovery of predictive anticancer targets.

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Studies of gene expression patterns in RER+ and RER- colon cancer cell lines

Biochemical Society Transactions ◽

10.1042/bst026s266 ◽

1998 ◽

Vol 26 (3) ◽

pp. S266-S266

Author(s):

Donncha Dunican ◽

Orna Tighe ◽

Anne Parle-McDermott ◽

David T. Croke

Keyword(s):

Gene Expression ◽

Colon Cancer ◽

Cell Lines ◽

Cancer Cell ◽

Expression Patterns ◽

Cancer Cell Lines ◽

Colon Cancer Cell ◽

Gene Expression Patterns ◽

Colon Cancer Cell Lines

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Over-expression of MicroRNA-122 Inhibits Proliferation and Induces Apoptosis in Colon Cancer Cells

MicroRNA ◽

10.2174/2211536609666201209152228 ◽

2020 ◽

Vol 09 ◽

Author(s):

Sarubala Malayaperumal ◽

Sushmitha Sriramulu ◽

Antara Banerjee ◽

Surajit Pathak

Keyword(s):

Gene Expression ◽

Colon Cancer ◽

Cell Proliferation ◽

Cell Lines ◽

Cancer Cell ◽

Cancer Cell Lines ◽

Colon Cancer Cell ◽

Transfected Cells ◽

Colon Cancer Cell Lines ◽

And Migration

Background: MicroRNA, a non-coding RNA molecule plays a vital role in post transcriptional gene expression. MicroRNA-122, a liver specific microRNA was found to be downregulated in liver cancer and it’s associated with hepatocarcinogenesis. Being confirmed as tumor suppressor microRNA in liver carcinogenesis, we aimed to study the expression of microRNA-122 in Colon cancer cell lines and also the role of microRNA-122 in cell proliferation, invasion and migration of colon cancer cells. Methods: The expression of microRNA-122 is quantified using qRT-PCR by TaqMan universal primers. Colon cancer cell lines (SW480, SW620, HCT116) were transfected with microRNA-122 mimics and further studied for determining cell proliferation using CCK-8 kit, migration using Scratch assay, invasion using Transwell assay, apoptosis using Annexin-V FITC kit, and also gene expression. Results: Gene expression results displayed decreased expression microRNA-122 in colon cancer cell lines. Transfection with microRNA-122 mimics impaired the cell proliferation and migration compared with control. FACS analysis confirmed that the percentage of microRNA-122 mimic transfected cells undergoing early apoptosis was increased. Gene expression of AEG-1, PI3K, CDK6, PCNA were found to be downregulated in microRNA-122 overexpressed cells. Migratory and invasion potential of transfected cells was lessened in mimic transfected cells compared to control. Conclusion: The overexpression of microRNA-122 inhibited the cellular proliferation, migration, invasion and increased percentage of cells undergoing early apoptosis suggesting its anti-cancer potential. Studying the role of microRNA-122 and its interactions with oncogenes might pave a way to understand the underlying mechanism in colon cancer.

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Isolation of Cardamonin and Pinostrobin Chalcone from the Rhizomes of Boesenbergia rotunda (L.) Mansf. and their Cytotoxic Effects on H-29 and MDA-MB-231 Cancer Cell Lines

The Natural Products Journal ◽

10.2174/2210315509666190117151542 ◽

2019 ◽

Vol 9 (4) ◽

pp. 341-348 ◽

Cited By ~ 4

Author(s):

Ibrahim Awad Mohammed ◽

Muhammad Nadeem Akhtar ◽

Foo Jhi Biau ◽

Yin Sim Tor ◽

Seema Zareen ◽

...

Keyword(s):

Breast Cancer ◽

Colon Cancer ◽

Cell Lines ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Chemical Constituents ◽

Cancer Cell Lines ◽

Colon Cancer Cell ◽

Colon Cancer Cell Lines ◽

Ht 29

Background: Breast cancer and human colon cancer are the most common types of cancer in females and males, respectively. Breast cancer is the most common type of cancer after lung and colon cancers. Natural products are an important source for drug discovery. Boesenbergia rotunda (L.) Mansf. is commonly known as finger root, belonging to the Zingiberaceae family. Objective: The aim of this study to isolate some natural compounds from the rhizomes of B. rotunda (L.) Mansf., and to investigate their cytotoxicity against the human triple-negative breast cancer cell (MDA-MB-231) and HT-29 colon cancer cell lines. Methods: The dried rhizomes of B. rotunda were extracted with methanol. The methanolic extract was further used for solvent-solvent extraction. Bioassay-guided extraction and isolation of the rhizomes of the B. rotunda exhibited cytotoxic properties of hexane and dichloromethane fractions. Results: Six major chemical constituents, pinostrobin (1), pinostrobin chalcone (2), cardamonin (3), 4,5-dihydrokawain (4), pinocembrin (5), and alpinetin (6) were isolated from the rhizomes of the B. rotunda. All the chemical constituents were screened against the human triple-negative breast cancer cell (MDA-MB-231) and HT-29 colon cancer cell lines. The compound cardamonin (3) (IC50 = 5.62±0.61 and 4.44±0.66 µg/mL) and pinostrobin chalcone (2), (IC50 = 20.42±2.23 and 22.51±0.42 μg/mL) were found to be potent natural cytotoxic compounds against MDA-MB-231 and HT-29 colon cancer cell lines, respectively. Conclusion: Cardamonin (3) and pinostrobin chalcone (2) were found to be the most potential natural compounds against breast cancer cell line MDA-MB-231 and colon cancer HT-29 cell line.

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Reactivity of Monoclonal Antibodies Directed against Lung Cancer Antigens with Human Lung, Breast and Colon Cancer Cell Lines

Disease Markers ◽

10.1155/1993/619781 ◽

1993 ◽

Vol 11 (5-6) ◽

pp. 225-237

Author(s):

Udo Schumacher ◽

Dhia Mukthar ◽

Thomas Schenker

Keyword(s):

Breast Cancer ◽

Lung Cancer ◽

Colon Cancer ◽

Cell Lines ◽

Cancer Cell ◽

Cancer Cell Lines ◽

Colon Cancer Cell ◽

Breast Cancer Cell Lines ◽

Cancer Antigens ◽

Colon Cancer Cell Lines

A panel of monoclonal antibodies (n=72 including controls) directed against lung cancer antigens was screened immunohistochemically against a panel of seven human lung cancer cell lines (including small cell carcinoma, squamous cell carcinoma, adenocarcinoma and mesothelioma), six human breast cancer cell lines and one human colon cancer cell line, The majority of the antibodies (n=42) reacted also with antigens present on breast and colon cancer cell lines, This cross reactivity especially between lung and breast cancer cell lines is not altogether unexpected since antigens common to breast and lung tissue including their neoplasms such as MUC1 antigen have been described, Our results indicate that epitopes shared by lung and breast cancers are probably more common than previously thought. The relevance for prognosis and therapy of these shared antigens, especially as disease markers in breast cancer, has to be investigated.

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