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

Bai, Shan; Feng, Qiang; Pan, Xinyan; Zou, Hong; Chen, Hao-Bin; Wang, Peng; Hong, Yaping; Song, Shuling; Yang, Ju-Lun

doi:10.3892/ijmm.2017.2903

Cited by 12 publications

(7 citation statements)

References 43 publications

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“…We found a significant overexpression of members of the Ras oncogene family HRAS and KRAS (known for their prominent roles in various types of cancer (e.g. [ 44 , 45 ]. MAP2K1 (mitogen-activated kinase 1), part of the RAS/MAPK pathways, which informs the cell nucleus about the extracellular chemical environment was also up-regulated.…”

Section: Resultsmentioning

confidence: 99%

Gene master regulators of papillary and anaplastic thyroid cancers

et al. 2017

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We hypothesize that distinct cell phenotypes are governed by different sets of gene master regulators (GMRs) whose strongly protected (by the homeostatic mechanisms) abundance modulates most cell processes by coordinating the expression of numerous genes from the corresponding functional pathways. Gene Commanding Height (GCH), a composite measure of gene expression control and coordination, is introduced to establish the gene hierarchy in each phenotype. If the hypothesis is true, than one can selectively destroy cancer nodules from a heterogeneous tissue by altering the expression of genes whose GCHs are high in cancer but low in normal cell phenotype. Here, we test the hypothesis and show its utility for the thyroid cancer (TC) gene therapy. First, we prove that malignant and cancer free surrounding areas of a surgically removed papillary TC (PTC) tumor are governed by different GMRs. Second, we show that stable transfection of a gene induces larger transcriptomic alterations in the cells where it has higher GCH than in other cells. For this, we profiled the transcriptomes of the papillary BCPAP and anaplastic 8505C TC cell lines before and after stable transfection with NEMP1, DDX19B, PANK2 or UBALD1. The four genes were selected to have similar expression levels but significantly different GCH scores in the two cell lines before transfection. Indeed, each of the four genes triggered larger alterations in the cells where they had larger GCH. Our results prove the feasibility of a personalized gene therapy approach that selectively targets the cancer cells from a tissue.

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Section: Resultsmentioning

confidence: 99%

Gene master regulators of papillary and anaplastic thyroid cancers

et al. 2017

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“…MAPK and PI3K pathways can communicate once Ras activates both Raf and PI3K (Carracedo & Pandolfi, 2008). Mutations in the Ras protein result in a constitutive activation of Ras (GTP‐bound active form) forming the mutant p21Ras (Bai et al, 2017). p21Ras overexpression plays an important carcinogenic role as it induces the activation of a kinase cascade (Bos, 1995).…”

Section: Resultsmentioning

confidence: 99%

Anticancer activity of limonene: A systematic review of target signaling pathways

Araújo-Filho

Santos

Carvalho

et al. 2021

Phytotherapy Research

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Limonene (LIM) is a monoterpene, which is abundant in essential oils of Citrus fruits peels (Rutaceae). More recently, LIM, as a potential natural anticancer compound, has attracted major attention and exerted a chemopreventive activity, stimulating the detoxification of carcinogenic compounds and limiting tumor growth and angiogenesis in various cancer models. Twenty‐six (26) articles were selected based on previously established criteria. Anticancer activity of LIM was related to the inhibition of tumor initiation, growth, and angiogenesis and the induction of cancer cells apoptosis. LIM was able to increase Bax expression, release cytochrome c, and activate the caspase pathway. In addition, LIM increased the expression of p53 and decreased the activity of Ras/Raf/MEK/ERK and PI3K/Akt pathways. LIM also decreased the expression of VEGF and increased the activities of the Man‐6‐P / IGF2R and TGF‐βIIR receptors. These results highlight LIM as an abundant natural molecule with low toxicity and pleiotropic pharmacological activity in cancer cells, targeting various cell‐signaling pathways critically involved in the initiation, growth, and chemoresistance of cancer cells.

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“…The p53 gene is the most widely studied tumor suppressor gene (38). The p21 gene is a product of the Ras proto-oncogene and its upregulation is closely associated with the development of colorectal cancer (39). However, the relationship between p21 and breast cancer remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Anticancer bioactive peptide combined with docetaxel and its mechanism in the treatment of breast cancer

Gao

2020

Exp Ther Med

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Breast cancer remains a worldwide public-health issue. Novel drugs that increase the sensitivity and reduce the toxic side effects of chemotherapeutic agents are urgently required. The present study investigated the effect and mechanism of the short-term intermittent administration of an anticancer bioactive peptide (ACBP), docetaxel (DTX), ACBP combined with DTX (MIX) and ACBP combined with low dose DTX (L-MIX) to nude mice bearing human breast cancer tumors. The body weight, tumor length, tumor diameter, diet and water consumption of the tumor-bearing nude mice were calculated. The protein and mRNA expression levels of p53, p21 and Ki67 were detected via immunohistochemistry and reverse transcription-quantitative PCR, respectively. The results revealed that the activity level of each group of mice was consistent. However, the food and water consumption of the ACBP group was significantly increased compared with the NS group. Compared with the normal saline group, the tumor weights and volumes of the treatment groups were significantly decreased, indicating an inhibitory effect of the treatment. However, the MIX group exhibited lower tumor weights and volumes compared with the ACBP and DTX groups. Furthermore, no significant cell necrosis, edema or inflammatory cell infiltration was observed upon hematoxylin & eosin staining of the liver and spleen in all groups. The results also revealed that the p21, p53 and Ki67 protein and mRNA levels were decreased in the ACBP, DTX and MIX groups compared with the control group. Additionally, when compared with those in the MIX and L-MIX groups, the p21 and Ki67 protein, and p53 and Ki67 mRNA levels in the ACBP and DTX groups were significantly increased. The results suggested that the short-term intermittent use of ACBP alone had an inhibitory effect on tumor growth and improved the food and water consumption of tumor-bearing nude mice. Furthermore, the combination of ACBP and DTX reduced toxic side effects and the dosage requirement of drugs to achieve therapeutic effects on the tumor-bearing nude mice. Therefore, the antitumor effect of ACBP may be associated with the improvement of immune function in tumor-bearing nude mice and ACBP may serve an antitumor role via the p53-p21 signaling pathway in breast cancer.

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

Cited by 12 publications

References 43 publications

Gene master regulators of papillary and anaplastic thyroid cancers

Gene master regulators of papillary and anaplastic thyroid cancers

Anticancer activity of limonene: A systematic review of target signaling pathways

Anticancer bioactive peptide combined with docetaxel and its mechanism in the treatment of breast cancer

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