The role of p53 protein family in gastrointestinal malignancies

Zaika, Alexander; El–Rifai, Wael

doi:10.1038/sj.cdd.4401897

Cited by 31 publications

(41 citation statements)

References 25 publications

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“…Of note, mice deficient in SHP or FXR, which show chronically elevated levels of BAs, are susceptible to liver and colorectal tumor formation (30)(31)(32)(33)(34), and BAs have also been suggested to play a causative role in human gastrointestinal cancers (10). Thus, it will be interesting to further investigate whether the p53-triggered decrease in BA levels represents a previously unrecognized avenue that p53 utilizes to exert its tumor suppression activity against liver and gastrointestinal cancers (35,36).…”

Section: Discussionmentioning

confidence: 99%

Tumor suppressor p53 regulates bile acid homeostasis via small heterodimer partner

Kim

Lee

2011

Proc. Natl. Acad. Sci. U.S.A.

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Metabolic changes in cancer have been observed for almost a century. The mechanisms underlying these changes have begun to emerge from the recent studies implicating the tumor suppressor p53 in multiple metabolic pathways. The ability of p53 to regulate metabolism may also play important roles in the physiology of normal cells and organs. Here we demonstrate that p53 lowers bile acid (BA) levels under both normal and stressed conditions primarily through up-regulating expression of small heterodimer partner, a critical inhibitor of BA synthesis. Our results uncover a unique metabolic regulatory axis that unexpectedly couples p53 to BA homeostasis. Our results also warrant future studies to investigate a possible role of this axis in the tumor suppression by p53, because excessive quantities of BAs are cytotoxic and can cause liver damage and promote gastrointestinal cancers.

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Section: Discussionmentioning

confidence: 99%

Tumor suppressor p53 regulates bile acid homeostasis via small heterodimer partner

Kim

Lee

2011

Proc. Natl. Acad. Sci. U.S.A.

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“…In particular, it emphasizes that there is a tight link between developmental processes and tumorigenesis. 9 Indeed, there is mounting evidence that p63 and p73 play an important role in DNA damage controlling cell cycle arrest and apoptosis ( Fig. 1) and in human cancer, [10][11][12][13][14][15][16][17][18] although their precise roles in tumorigenesis remain to be clarified.…”

Section: P63 In Cancer and Apoptosis Regulationmentioning

confidence: 99%

TAp63 and ΔNp63 in Cancer and Epidermal Development

et al. 2007

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“…HP53 plays an important role in gastrointestinal cancers [15]. Jackson et al analysed HP53 mutation in plasma and liver tumour samples, and found a correlation between the occurrence of plasma and tumour mutations of the HP53 gene.…”

Section: Discussionmentioning

confidence: 99%

Proinflammatory cytokines (IL-6, IL-18) and apoptotic factors (HP 53, survivin) in patients with alcoholic liver cirrhosis

Prystupa¹,

Kiciński²,

Sak³

et al. 2017

J Pre Clin Clin Res.

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and apoptotic factors (HP 53, survivin) in patients with alcoholic liver cirrhosis. J Pre-Clin Clin Res. 2017;11(1):1-5. doi: 10.26444/ jpccr/75134 AbstractBackground. Apoptosis is involved in the pathogenesis of alcoholic liver cirrhosis. Its development can be triggered by an inflammatory process. In the present study, levels of apoptotic factors -survivin human protein p53 (HP 53) and IL-6, IL-18 were determined according to the stage of liver cirrhosis. Material and methods. Seventy patients with alcoholic liver cirrhosis, treated in various hospitals of the Lublin region, Poland were included in the study. Serum levels of IL-6, IL-18, HP53 and survivin were determined by the enzyme-linked immunosorbent assay (ELISA) technique. Results. The serum level of survivin in patients with alcoholic liver cirrhosis was not statistically different from that found in the control group. The level of HP53 was significantly higher in the group of patients with alcoholic liver cirrhosis compared to the control group (16.53±22.69 vs. 0.39±1.31 U/ml; p<0.001). Likewise, the level of IL-6 was significantly higher in the group of patients with alcoholic liver cirrhosis compared to the control group (33.83±41.78 vs. 0.88 ± 0.56 pg/ml; p<0.001). Moreover, the level of IL-18 was significantly higher in the group of patients with liver cirrhosis compared to the control group (23.96±31.07 vs. 5.3±8.6 pg/ml; p<0.001). Conclusion. In conclusion, increased serum levels of IL-6 and IL-18 were demonstrated in patients with alcoholic liver cirrhosis. Moreover, the liver cirrhosis patients had elevated levels of HP53, which is a marker of apoptosis. Our results did not demonstrate the correlation between the levels of apoptosis markers (survivin, HP53) and the levels of cytokines (IL-6, IL-18) in the blood serum.

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The role of p53 protein family in gastrointestinal malignancies

Cited by 31 publications

References 25 publications

Tumor suppressor p53 regulates bile acid homeostasis via small heterodimer partner

Tumor suppressor p53 regulates bile acid homeostasis via small heterodimer partner

TAp63 and ΔNp63 in Cancer and Epidermal Development

Proinflammatory cytokines (IL-6, IL-18) and apoptotic factors (HP 53, survivin) in patients with alcoholic liver cirrhosis

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