Hepatotoxin-Induced Changes in the Adult Murine Liver Promote MYC-Induced Tumorigenesis

Beer, Shelly; Komatsubara, Kimberly M.; Bellovin, David I.; Kurobe, Masashi; Sylvester, Karl G.; Felsher, Dean W.

doi:10.1371/journal.pone.0002493

Cited by 40 publications

(49 citation statements)

References 31 publications

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“…CCl4 is diluted 1:10 in corn oil (Sigma), and administered IP at a dose of 0.5 ml/kg of mouse as described previously (Beer et al, 2008). Mice were injected and monitored twice per week.…”

Section: Methodsmentioning

confidence: 99%

Suppression of the SWI/SNF Component Arid1a Promotes Mammalian Regeneration

et al. 2016

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SUMMARY Mammals have partially lost the extensive regenerative capabilities of some vertebrates, possibly as a result of chromatin-remodeling mechanisms that enforce terminal differentiation. Here, we show that deleting the SWI/SNF component Arid1a substantially improves mammalian regeneration. Arid1a expression is suppressed in regenerating tissues, and genetic deletion of Arid1a increases tissue repair following an array of injuries. Arid1a deficiency in the liver increases proliferation, reduces tissue damage and fibrosis, and improves organ function following surgical resection and chemical injuries. Hepatocyte-specific deletion is also sufficient to increase proliferation and regeneration without excessive overgrowth, and global Arid1a disruption potentiates soft tissue healing in the ear. We show Arid1a loss reprograms chromatin to restrict promoter access by transcription factors such as C/ebpα, which enforces differentiation, and E2F4, which suppresses cell cycle reentry. Thus, epigenetic reprogramming mediated by deletion of a single gene improves mammalian regeneration and suggests strategies to promote tissue repair after injury.

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“…CCl4 is diluted 1:10 in corn oil (Sigma), and administered IP at a dose of 0.5 ml/kg of mouse as described previously (Beer et al, 2008). Mice were injected and monitored twice per week.…”

Section: Methodsmentioning

confidence: 99%

Suppression of the SWI/SNF Component Arid1a Promotes Mammalian Regeneration

et al. 2016

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“…Thus, toxins or carcinogens associated with the activation of cellular proliferation can cooperate with MYC to induce tumorigenesis (Beer et al 2008). Similarly, autocrine mechanisms involving the expression of transforming growth factor-a as well as other cytokines are critical in tumor initiation and maintenance, as described below (Calvisi and Thorgeirsson 2005;Cavin et al 2005).…”

Section: Myc Cooperates To Induce Tumorigenesismentioning

confidence: 99%

MYC Activation Is a Hallmark of Cancer Initiation and Maintenance

Gabay

Felsher

2014

Cold Spring Harbor Perspectives in Medicine

643

572

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The MYC proto-oncogene has been implicated in the pathogenesis of most types of human tumors. MYC activation alone in many normal cells is restrained from causing tumorigenesis through multiple genetic and epigenetically controlled checkpoint mechanisms, including proliferative arrest, apoptosis, and cellular senescence. When pathologically activated in a permissive epigenetic and/or genetic context, MYC bypasses these mechanisms, enforcing many of the "hallmark" features of cancer, including relentless tumor growth associated with DNA replication and transcription, cellular proliferation and growth, protein synthesis, and altered cellular metabolism. MYC mandates tumor cell fate, by inducing stemness and blocking cellular senescence and differentiation. Additionally, MYC orchestrates changes in the tumor microenvironment, including the activation of angiogenesis and suppression of the host immune response. Provocatively, brief or even partial suppression of MYC back to its physiological levels of activation can result in the restoration of intrinsic checkpoint mechanisms, resulting in acute and sustained tumor regression, associated with tumor cells undergoing proliferative arrest, differentiation, senescence, and apoptosis, as well as remodeling of the tumor microenvironment, recruitment of an immune response, and shutdown of angiogenesis. Hence, tumors appear to be "addicted" to MYC because of both tumor cellintrinsic, cell-autonomous and host-dependent, immune cell-dependent mechanisms. Both the trajectory and persistence of many human cancers require sustained MYC activation. Multiscale mathematical modeling may be useful to predict when tumors will be addicted to MYC. MYC is a hallmark molecular feature of both the initiation and maintenance of tumorigenesis.

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“…Therefore, abnormal expression of related genes plays a crucial role in carcinogenesis. Transcription factor involved in regulating cell proliferation, differentiation, and apoptosis [10] is encoded by c-myc proto-oncogene. Abnormal changes in mRNA expression and DNA methylation of p16 and c-myc are therefore, the two important stimulatory factors in the development of liver cancer.…”

Section: Liver Cancermentioning

confidence: 99%

Betaine Supplementation for Various Clinical Disorders

Jayalakshmi

Vanitha

2017

Asian J Pharm Clin Res

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Betaine is distributed widely in animals, plants, and microorganisms and rich dietary sources include seafood, especially marine invertebrates. Betaine is N-trimethylated amino acid called as glycine betaine. It is a by-product. Betaine aldehyde is produced when choline dehydrogenase acts on choline, then betaine aldehyde is oxidized to form betaine by aldehyde dehydrogenase. Metabolic derived betaines possess various functions in our body in which they act as methyl donor which helps in liver function, detoxication, and cellular functions. It plays an important role in fat metabolism. Recent research found that betaine can convert homocysteine to cysteine thus they prevent heart disease. Choline is oxidized to betaine in liver and kidney. Intracellular betaine serves as an osmolyte that regulates cell volume and tissue integrity. Betaine not only plays as an osmolyte but also play a major role in the protection of the liver and other tissues. Consequently, it has been proposed that betaine has significant nutrient for prevention of chronic disease. Betaine has been shown to protect internal organs, improve vascular risk factors, and enhance performance. Databases of betaine content in food are being developed for correlation with population health studies. This review focuses on the aspects of wide research field with emphasis on a recent data relevant to various human diseases.

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Hepatotoxin-Induced Changes in the Adult Murine Liver Promote MYC-Induced Tumorigenesis

Cited by 40 publications

References 31 publications

Suppression of the SWI/SNF Component Arid1a Promotes Mammalian Regeneration

Suppression of the SWI/SNF Component Arid1a Promotes Mammalian Regeneration

MYC Activation Is a Hallmark of Cancer Initiation and Maintenance

Betaine Supplementation for Various Clinical Disorders

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