Assessment of Differential Gene Expression Patterns in Human Colon Cancers

Abstract

ObjectiveTo use a novel genomic approach to determine differential gene expression patterns in colon cancers of different metastatic potential. Summary Background DataColorectal cancer is the third leading cause of cancer deaths in the United States; despite aggressive treatment strategies, the 5-year survival rate for metastatic cancer has not changed in 50 years. The analysis of changes in gene expression patterns associated with metastasis may provide new treatment strategies. MethodsHuman colon cancer cells KM12C (derived from a Dukes B colon cancer), KML4A (a metastatic variant derived from KM12C), and KM20 (derived from a Dukes D colon cancer) were extracted for RNA. In addition, RNA was extracted from normal colon, primary cancer, and liver metastasis in a patient with metastatic colon cancer. Gene expression patterns for approximately 1,200 human genes were analyzed and compared by cDNA array techniques. ResultsOf the roughly 1,200 genes assessed in the KM cell lines, 9 genes were noted to have a more than threefold change in expression (either increased or decreased) in the more metastatic KML4A and KM20 cells compared with KM12C. Assessment of tissues from a patient with metastatic colon cancer demonstrated a more than threefold change in the expression of 14 genes in the primary cancer and liver metastasis compared with normal mucosa. ConclusionsUsing cDNA expression array technology, the authors identified genes with expression levels that are altered with metastasis. The ability to analyze and compare the expression patterns of multiple genes simultaneously provides a powerful technique to identify potential molecular targets for novel therapeutic strategies.

Withaferin A sensitizes TRAIL-induced apoptosis through reactive oxygen species-mediated up-regulation of death receptor 5 and down-regulation of c-FLIP

“…It is generally recognized that c-FLIP protein levels can be transcriptionally regulated through the nuclear factor-κB or c-fos pathway [9,39,40] or by ubiquitin-and caspase-mediated degradation [37,[41][42][43]. Recent reports showed that Wit A has a strong ability not only to block completely the binding of the transcription factor to DNA but also to induce the cleavage of NF-κB [4,10]. In our system, c-FLIP L and c-FLIP S mRNA expression was down-regulated by Wit A treatment through inhibition of the NF-κB signaling pathways.…”

“…Recently, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been paid attention as a potential anti-cancer drug, because it induces apoptosis in a wide variety of cancer cells but not in most normal human cell types [2,3]. However, recent studies have shown that some cancer cells, including malignant RCC and hepatocellular carcinoma, are resistant to the apoptotic effects of TRAIL [4,5]. Therefore, single treatment with TRAIL may not be sufficient for the treatment of various malignant tumor cells.…”

Identification of Disease-specific Genes in Chronic Pancreatitis Using DNA Array Technology

“…One of the main points of interest is the analysis of genes involved in carcinogenesis. Up to now, several different human tumors, such as ovarian cancer, 34 lung cancer, 35,36 breast cancer, [37][38][39] colon cancer, 40 prostate cancer, [41][42][43] rhabdomyosarcoma, 44 melanoma, 45 and head and neck cancers, 46,47 have been investigated by DNA array analysis to identify cancer-specific genes, genes involved in metastasis formation, 48 and genes that regulate the response toward chemotherapy. 49 The present study is the first, to our knowledge, that investigates differential expression using DNA arrays in a chronic inflammatory disorder: CP.…”

Mithramycin A sensitizes cancer cells to TRAIL-mediated apoptosis by down-regulation of XIAP gene promoter through Sp1 sites

“…Targeting death receptors, especially DR4 or DR5, to trigger apoptosis in tumor cells is an attractive concept for cancer therapy because tumor necrosis factor-a -related apoptosis-inducing ligand (TRAIL) has been shown to induce apoptosis in a wide variety of cancer cells, including renal cancer cells, whereas most normal human cell types are resistant to TRAILinduced cell death, which is supported by the presence of large numbers of decoy receptors on normal cells (3,4). However, recent studies have shown that some cancer cells are resistant to the apoptotic effects of TRAIL (5,6). TRAILresistant cancer cells can be sensitized by chemotherapeutic drugs in vitro, indicating that combination therapy may be a possibility.…”