Relationship Between Expression of ras p21 Oncoprotein and Mutation Status of the K-ras Gene in Sporadic Colorectal Cancer Patients in Tunisia

Sammoud, Souraya; Khiari, M.; Amara, Semeh; Lounis, Mohamed Amine; Chaar, Ines; Amira, Abbes; Lilia, Kriaa; Khalfallah, Tahar; Mzabi, Sabeh; Bouraoui, Saâdia

doi:10.1097/pai.0b013e3182240de1

Cited by 18 publications

(30 citation statements)

References 21 publications

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“…The results showed that there was almost no p21Ras expression in normal colorectal mucosa, but high level expression of p21Ras in CRC and colorectal intraepithelial neoplasia. Together with the reported data (15,43–46), we confirmed that p21Ras overexpression is an important event in colorectal carcinogenesis and plays a major role in the development of CRC.…”

Section: Discussionsupporting

confidence: 89%

Overexpression of wild-type p21Ras plays a prominent role in colorectal cancer

Bai

Feng

Pan

et al. 2017

International Journal of Molecular Medicine

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Colorectal cancer (CRC) is the most common gastrointestinal type of cancer. The overexpression of Ras proteins, particularly p21Ras, are involved in the development of CRC. However, the subtypes of the p21Ras proteins that are overexpressed and the mutation status remain unknown restricting the development of therapeutic antibodies targeting p21Ras proteins. The present study aimed to investigate the mutation status of ras genes associated with Ras proteins that are overexpressed in CRC and explore whether or not wild-type p21Ras could be a target for CRC therapy. p21Ras expression was examined immunohistochemically in normal colorectal epithelium, benign lesions and malignant colorectal tumor tissues by monoclonal antibody (Mab) KGH-R1 which is able to react with three types of p21Ras proteins: H-p21Ras, N-p21Ras and K-p21Ras. Then, the expression levels of p21Ras subtypes were determined in CRC by a specific Mab for each p21Ras subtype. Mutation status of ras genes in p21Ras-overexpressing CRC was detected by DNA sequencing. There was rare p21Ras expression in normal colorectal epithelium but a high level of p21Ras expression in CRC, with a significant increase from normal colorectal epithelium to inflammatory polyps, low-grade intraepithelial neoplasia, high-grade intraepithelial neoplasia and invasive colorectal adenocarcinoma, respectively. Overexpression of K-p21Ras was found in all CRC tissues tested, overexpression of N-p21Ras was found in 85.7% of the CRC tissues, while H-p21Ras expression was not found in any CRC tissue. DNA sequencing showed that there were no K-ras mutations in 60% of the K-p21Ras-overexpressing CRC, while 40% of the CRC tissues harbored K-ras mutations. N-ras mutations were not found in any N-p21Ras-overexpressing CRC. Our findings indicate that overexpression of wild-type p21Ras may play a prominent role in the development of CRC in addition to ras mutations and could be a promising target for CRC therapy.

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Section: Discussionsupporting

confidence: 89%

Overexpression of wild-type p21Ras plays a prominent role in colorectal cancer

Bai

Feng

Pan

et al. 2017

International Journal of Molecular Medicine

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“…K-ras is known as an oncogene (Izadi-Mood et al, 2013;Sammoud et al, 2012) which has been reported to be involved especially in lung cancer (Fatima and Yee, 2014;Rotella et al, 2014). Although lung cancer induced by radon has been confirmed by epidemiology studies (Choi and Mazzone, 2014;Melloni, 2014;Edwards et al, 2014), the role of K-ras gene in radon carcinogenesis is not yet identified.…”

Section: Discussionmentioning

confidence: 95%

Down-regulation of let-7 microRNA increased K-ras expression in lung damage induced by radon

Chen

Wang

et al. 2015

Environmental Toxicology and Pharmacology

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“…Often, results were not statistically significant, possibly due to lack of power. Eighteen studies were included in an analysis on KRAS status in MC and NMC and KRAS mutations were found in MC more frequently (RR 1.27, 95% CI 1.14–1.41; Figure ) .…”

Section: Molecular Determinants In MCmentioning

confidence: 99%

The molecular background of mucinous carcinoma beyond MUC2

Hugen

Simons

Halilović

et al. 2014

The Journal of Pathology CR

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The increasing interest of the oncology community in tumour classification and prediction of outcome to targeted therapies has put emphasis on an improved identification of tumour types. Colorectal mucinous adenocarcinoma (MC) is a subtype that is characterized by the presence of abundant extracellular mucin that comprises at least 50% of the tumour volume and is found in 10–15% of colorectal cancer patients. MC development is poorly understood, however, the distinct clinical and pathological presentation of MC suggests a deviant development and molecular background. In this review we identify common molecular and genetic alterations in colorectal MC. MC is characterized by a high rate of MUC2 expression. Mutation rates in the therapeutically important RAS/RAF/MAPK and PI3K/AKT pathways are significantly higher in MC compared with non‐mucinous adenocarcinoma. Furthermore, mucinous adenocarcinoma shows higher rates of microsatellite instability and is more frequently of the CpG island methylator phenotype. Although the majority of MCs arise from the large intestine, this subtype also develops in other organs, such as the stomach, pancreas, biliary tract, ovary, breast and lung. We compared findings from colorectal MC with tumour characteristics of MCs from other organs. In these organs, MCs show different mutation rates in the RAS/RAF/MAPK and PI3K/AKT pathways as well, but a common mucinous pathway cannot be identified. Identification of conditions and molecular aberrations that are associated with MC generates insight into the aetiology of this subtype and improves understanding of resistance to therapies.

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Relationship Between Expression of ras p21 Oncoprotein and Mutation Status of the K-ras Gene in Sporadic Colorectal Cancer Patients in Tunisia

Abstract: Genetic K-ras alterations were rather low in the Tunisian population, but further study is necessary to unravel the molecular background of CRC.

Cited by 18 publications

References 21 publications

Overexpression of wild-type p21Ras plays a prominent role in colorectal cancer

Overexpression of wild-type p21Ras plays a prominent role in colorectal cancer

Down-regulation of let-7 microRNA increased K-ras expression in lung damage induced by radon

The molecular background of mucinous carcinoma beyond MUC2

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