Topic
Carcinogenesis
About: Carcinogenesis is a research topic. Over the lifetime, 60368 publications have been published within this topic receiving 3192599 citations. The topic is also known as: oncogenesis & tumorigenesis.
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TL;DR: The present study provides the first evidences that miR-143 is significant in suppressing colorectal cancer cell growth through inhibition of KRAS translation.
Abstract: Dysregulated expression of microRNAs (miRNAs) is associated with a variety of diseases, including colorectal cancer By comparing more than 200 miRNAs in 13 pairs of matched colorectal cancer and normal adjacent tissue samples through qRT-PCR and microarray analysis, we found a widespread disruption of miRNA expression during colorectal tumorigenesis In particular, among a panel of presumed targets generated by in silico analysis that may interact with these aberrantly expressed miRNAs, KRAS oncogene has been further experimentally validated as the target of miR-143 First, an inverse correlation between KRAS protein and miR-143 in vivo was found Second, KRAS expression in Lovo cells was significantly abolished by treatment with miR-143 mimic, whereas miR-143 inhibitor increased KRAS protein level Third, luciferase reporter assay confirmed that miR-143 directly recognize the 3'-untranslated region of KRAS transcripts Four, Lovo cells treated with miR-143 inhibitor showed a stimulated cell proliferation, whereas miR-143 overexpression had an opposite effect Finally, inhibition of KRAS expression by miR-143 inhibits constitutive phosphorylation of ERK1/2 Taken together, the present study provides the first evidences that miR-143 is significant in suppressing colorectal cancer cell growth through inhibition of KRAS translation
532 citations
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TL;DR: Results indicate arsenic can act as a carcinogen by inducing DNA hypomethylation, which in turn facilitates aberrant gene expression, and they constitute a tenable theory of mechanism in arsenic carcinogenesis.
Abstract: Inorganic arsenic, a human carcinogen, is enzymatically methylated for detoxication, consuming S-adenosyl-methionine (SAM) in the process. The fact that DNA methyltransferases (MeTases) require this same methyl donor suggests a role for methylation in arsenic carcinogenesis. Here we test the hypothesis that arsenic-induced initiation results from DNA hypomethylation caused by continuous methyl depletion. The hypothesis was tested by first inducing transformation in a rat liver epithelial cell line by chronic exposure to low levels of arsenic, as confirmed by the development of highly aggressive, malignant tumors after inoculation of cells into Nude mice. Global DNA hypomethylation occurred concurrently with malignant transformation and in the presence of depressed levels of S-adenosyl-methionine. Arsenic-induced DNA hypomethylation was a function of dose and exposure duration, and remained constant even after withdrawal of arsenic. Hyperexpressibility of the MT gene, a gene for which expression is clearly controlled by DNA methylation, was also detected in transformed cells. Acute arsenic or arsenic at nontransforming levels did not induce global hypomethylation of DNA. Whereas transcription of DNA MeTase was elevated, the MeTase enzymatic activity was reduced with arsenic transformation. Taken together, these results indicate arsenic can act as a carcinogen by inducing DNA hypomethylation, which in turn facilitates aberrant gene expression, and they constitute a tenable theory of mechanism in arsenic carcinogenesis.
531 citations
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TL;DR: Aberrant or increased expression of cyclooxygenase (COX)‐2 has been implicated in the pathogenesis of many diseases including carcinogenesis and has been shown to be over‐expressed in some human cancers.
Abstract: Aberrant or increased expression of cyclooxygenase (COX)-2 has been implicated in the pathogenesis of many diseases including carcinogenesis. COX-2 has been shown to be over-expressed in some human cancers.
Employing semi-quantitative reverse transcription-PCR, immunoblotting, and immunohistochemistry we assessed COX-2 expression in samples of pair-matched benign and cancer tissue obtained from the same prostate cancer patient.
Mean levels of COX-2 mRNA were 3.4-fold higher in prostate cancer tissue (n = 12) compared with the paired benign tissue. The immunoblot analysis demonstrated that as compared to benign tissue COX-2 protein was over-expressed in 10 of 12 samples examined. Immunohistochemical analysis also verified COX-2 over-expression in cancer than in benign tissue.
To our knowledge, this is the first in vivo study showing an over-expression of COX-2 in prostate cancer. These data suggest that COX-2 inhibitors may be useful for prevention or therapy of prostate cancer in humans. Prostate 42:73–78, 2000. © 2000 Wiley-Liss, Inc.
530 citations
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TL;DR: The current evidence suggests that aneuploidy promotes tumorigenesis, at least at low frequency, but a definitive test has not yet been reported.
530 citations
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TL;DR: The role of TGF-β signaling in cell cycle arrest, apoptosis, EMT and cancer cell metastasis is considered and recent insights into the multistep and dynamically controlled process of T GF-β-induced EMT are highlighted.
Abstract: Transforming growth factor β (TGF-β) is a secreted cytokine that regulates cell proliferation, migration, and the differentiation of a plethora of different cell types. Consistent with these findings, TGF-β plays a key role in controlling embryogenic development, inflammation, and tissue repair, as well as in maintaining adult tissue homeostasis. TGF-β elicits a broad range of context-dependent cellular responses, and consequently, alterations in TGF-β signaling have been implicated in many diseases, including cancer. During the early stages of tumorigenesis, TGF-β acts as a tumor suppressor by inducing cytostasis and the apoptosis of normal and premalignant cells. However, at later stages, when cancer cells have acquired oncogenic mutations and/or have lost tumor suppressor gene function, cells are resistant to TGF-β-induced growth arrest, and TGF-β functions as a tumor promotor by stimulating tumor cells to undergo the so-called epithelial-mesenchymal transition (EMT). The latter leads to metastasis and chemotherapy resistance. TGF-β further supports cancer growth and progression by activating tumor angiogenesis and cancer-associated fibroblasts and enabling the tumor to evade inhibitory immune responses. In this review, we will consider the role of TGF-β signaling in cell cycle arrest, apoptosis, EMT and cancer cell metastasis. In particular, we will highlight recent insights into the multistep and dynamically controlled process of TGF-β-induced EMT and the functions of miRNAs and long noncoding RNAs in this process. Finally, we will discuss how these new mechanistic insights might be exploited to develop novel therapeutic interventions.
529 citations