Modulation of prostate cancer genetic risk by omega-3 and omega-6 fatty acids

Berquin, Isabelle M.; Min, You-Nong; Wu, Ruping; Wan, Jin; Perry, Donna L.; Cline, J. Mark; Thomas, Mike J.; Thornburg, Todd; Kulik, George; Smith, Alexis Nicole; Edwards, Iris J.; D’Agostino, Ralph; Zhang, Hao; Wu, Hong; Kang, Jing; Chen, Yong Q.

doi:10.1172/jci31494

Cited by 239 publications

(222 citation statements)

References 47 publications

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“…For example, based on an extensive body of literature indicating that dietary restriction is anti-tumorigenic, analyses of dietary restriction or low-fat diets on cancer progression in genetically engineered mice has revealed the PI3K-Akt signaling pathway as a molecular target for these dietary interventions (Berquin et al 2007;Kobayashi et al 2008;Kalaany and Sabatini 2009). Another promising agent is vitamin D, which has been suggested by ample epidemiological evidence to protect against tumorigenesis, but has displayed variable efficacy in clinical trials (Deeb et al 2007).…”

Section: Dietary and Lifestyle Factors In Cancer Preventionmentioning

confidence: 99%

Molecular genetics of prostate cancer: new prospects for old challenges

Shen¹,

2010

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Despite much recent progress, prostate cancer continues to represent a major cause of cancer-related mortality and morbidity in men. Since early studies on the role of the androgen receptor that led to the advent of androgen deprivation therapy in the 1940s, there has long been intensive interest in the basic mechanisms underlying prostate cancer initiation and progression, as well as the potential to target these processes for therapeutic intervention. Here, we present an overview of major themes in prostate cancer research, focusing on current knowledge of principal events in cancer initiation and progression. We discuss recent advances, including new insights into the mechanisms of castration resistance, identification of stem cells and tumor-initiating cells, and development of mouse models for preclinical evaluation of novel therapuetics. Overall, we highlight the tremendous research progress made in recent years, and underscore the challenges that lie ahead.

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Section: Dietary and Lifestyle Factors In Cancer Preventionmentioning

confidence: 99%

Molecular genetics of prostate cancer: new prospects for old challenges

Shen¹,

2010

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“…BAD is dephosphorylated in response to ZD1839, and primary mammary epithelial cultures derived from BAD-deficient mice proved resistant to the toxic effect of this drug. Likewise, loss-of-function studies in a mouse model of prostate cancer underscored a physiologically relevant role for BAD in tumor regression induced by omega-3 and omega-6 polyunsaturated fatty acids (Berquin et al, 2007). While BAD phosphorylation is a component of the survival program driven by the oncogenic activation of select kinases, BAD dephosphorylation may contribute to the pro-apoptotic effects of certain tumor suppressors.…”

Section: Bad and Tumor Cell Apoptosismentioning

confidence: 99%

BAD: undertaker by night, candyman by day

2008

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The BH3-only pro-apoptotic proteins are upstream sensors of cellular damage that selectively respond to specific, proximal death and survival signals. Genetic models and biochemical studies indicate that these molecules are latent killers until activated through transcriptional or post-translational mechanisms in a tissue-restricted and signal-specific manner. The large number of BH3-only proteins, their unique subcellular localization, protein-interaction network and diverse modes of activation suggest specialization of their damage-sensing function, ensuring that the core apoptotic machinery is poised to receive input from a wide range of cellular stress signals. The apoptotic response initiated by the activation of BH3-only proteins ultimately culminates in allosteric activation of pro-apoptotic BAX and BAK, the gateway proteins to the mitochondrial pathway of apoptosis. From activation of BH3-only proteins to oligomerization of BAX and BAK and mitochondrial outer membrane permeabilization, an intricate network of interactions between the pro-and anti-apoptotic members of the BCL-2 family orchestrates the decision to undergo apoptosis. Beyond regulation of apoptosis, multiple BCL-2 proteins have recently emerged as active components of select homeostatic pathways carrying other cellular functions. This review focuses on BAD, which was the first BH3-only protein linked to proximal survival signals through phosphorylation by survival kinases. In addition to findings that delineated the physiological role of BAD in apoptosis and its dynamic regulation by phosphorylation, studies pointing to new roles for this protein in other physiological pathways, such as glucose metabolism, are highlighted. By executing its 'day' and 'night' jobs in metabolism and apoptosis, respectively, BAD helps coordinate mitochondrial fuel metabolism and the apoptotic machinery.

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“…Furthermore, to determine the influence of n-6 and n-3 fatty acids on prostate cancer risk in animals with a defined genetic lesion (Pten-deletion), Chen and his colleagues crossed the fat-1 mice with prostate-specific Pten-knockout mice (a prostate cancer model) to generate compound mice (Pten-knockout plus fat-1) (10). They found that the hybrid mice (Pten-knockout plus fat-1, which have higher levels of n-3 fatty acids) had a significantly lower rate of tumor growth and survived longer compared to Pten-knockout mice (without fat-1) (10). Tumors from mice with high n-3 had lower proportions of phosphorylated Bad, resulting in increased cell apoptosis (10).…”

Section: Recent Studies Utilizing the Fat-1 Micementioning

confidence: 99%

Fat-1 transgenic mice: A new model for omega-3 research

Kang¹

2007

Prostaglandins, Leukotrienes and Essential Fatty Acids

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An appropriate animal model that can eliminate confounding factors of diet would be very helpful for evaluation of the health effects of nutrients such as n-3 fatty acids. We recently generated a fat-1 transgenic mouse expressing the C. elegans fat-1 gene encoding an n-3 fatty acid desaturase that converts n-6 to n-3 fatty acids (which is absent in mammals). The fat-1 transgenic mice are capable of producing n-3 fatty acids from the n-6 type, leading to abundant n-3 fatty acids with reduced levels of n-6 fatty acids in their organs and tissues, without the need of a dietary n-3 supply. Feeding an identical diet (high in n-6) to the transgenic and wild type littermates can produce different fatty acid profiles in these animals. Thus, this model allows well-controlled studies to be performed, without the interference of the potential confounding factors of diet. The transgenic mice are now being used widely and are emerging as a new tool for studying the benefits of n-3 fatty acids and the molecular mechanisms of their action.

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Modulation of prostate cancer genetic risk by omega-3 and omega-6 fatty acids

Cited by 239 publications

References 47 publications

Molecular genetics of prostate cancer: new prospects for old challenges

Molecular genetics of prostate cancer: new prospects for old challenges

BAD: undertaker by night, candyman by day

Fat-1 transgenic mice: A new model for omega-3 research

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