Genetics of colorectal cancer (Review)

Peddanna, N.; Mendis, Ruwani; Holt, Shawn E.; Verma, Ram S.

doi:10.3892/ijo.9.2.327

Cited by 11 publications

(13 citation statements)

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“…These observations rather suggest that Cdx-1 is a homeobox gene with oncogenic potential. The stimulation of Cdx-1 reported in this study by oncogenic ras in colonic Caco-2 cells is consistent with the onset of expression found in metaplasic areas of oesophagus and gastric cancers, since oncogenic ras activation is often associated with well di erentiated tumours of the upper digestive tract (Peddanna et al, 1995). Thus, during early events in the progression of normal colonic epithelium to adenoma, oncogenic ras activation would stimulate Cdx-1; additional genetic alterations may subsequently downregulate this gene during further progression to adenocarcinoma and distant metastasis, as observed by Silberg et al (1997), Mallo et al (1997) and Vider et al (1997).…”

Section: Discussionsupporting

confidence: 89%

Downregulation of the colon tumour-suppressor homeobox gene Cdx-2 by oncogenic ras

et al. 1999

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Constitutive activation of the ras proto-oncogene is a frequent and early event in colon cancers, but the downstream nuclear targets are not fully understood. The Cdx-1 and Cdx-2 homeobox genes play crucial roles in intestinal cell proliferation and di erentiation. In addition, Cdx-2 is a colonic tumour-suppressor gene, whereas Cdx-1 has oncogenic potential. Here, we show that constitutive activation of ras alters Cdx-1 and Cdx-2 expression in human colonic Caco-2 and HT-29 cells that harbour a normal ras proto-oncogene. Oncogenic ras downregulates Cdx-2 through activation of the PKC pathway and a decline in activity of the Cdx-2 promoter AP-1 site. This decline results from a PKC-dependent decrease in the relative expression of c-Jun, an activator of Cdx-2 transcription, compared to c-Fos, an inhibitor of Cdx-2. Unlike Cdx-2, Cdx-1 is upregulated by oncogenic ras and this e ect is mediated by activation of the MEK1 pathway. These results indicate that oncogenic ras activation has opposite e ects on Cdx-1 and Cdx-2 expression through distinct signalling pathways and they provide the ®rst evidence for a functional link between ras activation and the downregulation of the Cdx-2 tumour-suppressor gene in colon cancer cells.

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Section: Discussionsupporting

confidence: 89%

Downregulation of the colon tumour-suppressor homeobox gene Cdx-2 by oncogenic ras

et al. 1999

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“…Since the 5-year survival rate of patients who are diagnosed at an advanced stage is generally less than 10% (Peddanna et al, 1995), identification of sensitive diagnostic markers and development of novel therapeutic modalities other than surgery are of some urgency.…”

Section: Introductionmentioning

confidence: 99%

Comparison of gene-expression profiles between diffuse- and intestinal-type gastric cancers using a genome-wide cDNA microarray

et al. 2004

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Gastric cancer is the fourth leading cause of cancerrelated death in the world. Two histologically distinct types of gastric carcinoma, 'intestinal' and 'diffuse', have different epidemiological and pathophysiological features that suggest different mechanisms of carcinogenesis. A number of studies have investigated intestinal-type gastric cancers at the molecular level, but little is known about mechanisms involved in the diffuse type, which has a more invasive phenotype and poorer prognosis. To clarify the mechanisms that underlie its development and/or progression, we compared the expression profiles of 20 lasermicrobeam-microdissected diffuse-type gastric-cancer tissues with corresponding noncancerous mucosae by means of a cDNA microarray containing 23 040 genes. We identified 153 genes that were commonly upregulated and more than 1500 that were commonly downregulated in the tumors. We also identified a number of genes related to tumor progression. Furthermore, comparison of the expression profiles of diffuse-type with those of intestinal-type gastric cancers identified 46 genes that may represent distinct molecular signatures of each histological type. The putative signature of diffuse-type cancer exhibited altered expression of genes related to cellmatrix interaction and extracellular-matrix (ECM) components, whereas that of intestinal-type cancer represented enhancement of cell growth. These data provide insight into different mechanisms underlying gastric carcinogenesis and may also serve as a starting point for identifying novel diagnostic markers and/or therapeutic targets for diffuse-type gastric cancers.

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“…Patients with small and early cancer lesions who undergo surgical resection have a better chance of survival. However, most patients are diagnosed with advanced stage disease and the five-year survival rate is generally less than 10% (Peddanna et al, 1995).…”

mentioning

confidence: 99%

Comprehensive analysis of the gene expression profiles in human gastric cancer cell lines

Chen

Leung

et al. 2002

Oncogene

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Genetics of colorectal cancer (Review)

Cited by 11 publications

References 0 publications

Downregulation of the colon tumour-suppressor homeobox gene Cdx-2 by oncogenic ras

Downregulation of the colon tumour-suppressor homeobox gene Cdx-2 by oncogenic ras

Comparison of gene-expression profiles between diffuse- and intestinal-type gastric cancers using a genome-wide cDNA microarray

Comprehensive analysis of the gene expression profiles in human gastric cancer cell lines

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