Featured Research

from universities, journals, and other organizations

Dietary glucose affects the levels of a powerful oncogene in mice

Date:
November 15, 2012
Source:
Georgetown University Medical Center
Summary:
In this study, researchers help establish the mechanisms of why a low carbohydrate diet slows tumor growth in mice. The findings do not mean that cancer patients should cut back on the sugar in their diets, but it does pose questions about the consequences of diet on increased activity of an oncogene that drives tumor growth.

An animal study conducted by researchers at Georgetown Lombardi Comprehensive Cancer Center raises questions about the consequences of diet -- specifically glucose, the plant-based sugar that fuels cell life -- on increased activity of an oncogene that drives tumor growth.

In the study recently published online in the journal Cell Cycle, the scientists report, for the first time, that high levels of glucose in the diet of mice with cancer is linked to increased expression of mutant p53 genes. Normal p53 acts as a tumor suppressor, but many scientists believe that mutant p53 acts as an oncogene, pushing cancer growth. High levels of mutant p53 expression in a wide variety of human tumors has long been linked to cancer aggressiveness, resistance to therapy, worse outcomes and even relapse after therapy.

The findings do not mean that cancer patients should cut back on the sugar in their diets, says the study's senior investigator, Maria Laura Avantaggiati, M.D., associate professor of oncology at Georgetown Lombardi, part of Georgetown University Medical Center (GUMC).

"We have not studied the effect of glucose on cancer growth in humans, so we cannot make that link at this point," she says. "Furthermore, there are many different types of p53 mutations and we have studied only some of them. But if we can show that this is a generalized phenomenon, it could have important implications for care, and may help explain the observation that human diet does affect cancer treatment and growth."

Avantaggiati adds that the study tested different components of the diet and found that complete starvation, among other factors, did not have any effect on the levels of mutant p53 in laboratory-cultured cancer cells. She also adds that specific research examining if different components of the diet, aside from glucose, will contribute to the growth of tumors harboring p53 mutations is necessary.

Glucose restriction prompts cells to clear mutant protein

In the study, the researchers sought to understand how to reduce the levels of proteins generated by mutations of the p53 gene in tumors. The issue is important, Avantaggiati says, not only because the majority of human tumors contains too much mutant p53 protein, but also because researchers now believe that current chemotherapy drugs actually increase the amount of mutant p53 in cancer, leading to possible resistance to these drugs.

In the five-year study, conducted in collaboration with her GUMC colleagues and co-authors Chris Albanese, Ph.D., and Olga Rodriguez, M.D., Ph.D., the researchers studied the link between glucose restriction and autophagy in cultured cells. Autophagy is a process that clears a cell of damaged organelles and misfolded proteins -- proteins viewed to be dysfunctional.

"Mutant p53 proteins are misfolded, but they are usually not efficiently degraded. However, when autophagy is induced by glucose restriction, this process eliminates them, and this is what we were hoping to see," Avantaggiati says. But the process offers an additional bonus. Autophagy is usually turned-off by mutant p53, but because these cancer cells now contain very little p53 protein, autophagy marches on, chewing up proteins, pushing the cancer cell to die.

The researchers then conducted a series of studies to see if this link could be established in animal models. In a transgenic mouse model with mutant p53, they showed that in mice fed a low carbohydrate (low glucose) diet -- but one with a normal calorie load -- there was a significant decrease in the amount of mutant p53 protein in their tissues, compared to mice fed with a high carbohydrate diet.

This suggested that mutant p53 levels are sensitive to glucose restriction, but additional research was needed to determine whether this phenomenon had an impact upon tumor growth.

To help answer that question, other experiments were conducted to test the ability of human lung cancer cells, engrafted in mice, to grow when the animals were fed one of two diets -- low or high carbohydrates. In this case the researchers constructed a p53 mutant protein that was less susceptible to degradation by glucose restriction-induced autophagy.

They found that in the mice fed the low carbohydrate diet, the growth of tumors was blocked, but only when the tumors expressed the mutant p53 protein that could be degraded by autophagy. But when the artificial mutant p53 proteins could not be cleared, cancer growth proceeded regardless of the glucose content in the diet. This suggested that p53 mutant degradation is part of the reason why the low carbohydrate diet slows tumor growth, Avantaggiati says.

"This series of studies helps establish the mechanisms of why a low carbohydrate diet slows tumor growth," says Avantaggiati. "Glucose restriction triggers autophagy, a critical process for clearing the cell of detrimental, potentially damaging proteins or cellular debris that can eventually destroy the entire cancer cell. We believe that this process works more efficiently when mutant p53 is not around."

The findings are very compelling, she says, and should set the ground for investigating, in further depth, how glucose and various food components affect the levels of mutant p53 in tumors. "Various types of dietetic interventions have been shown to affect cancer growth, but no one had ever shown, before this study, that the amount of carbohydrates could affect the expression of mutant p53," Avantaggiati says. "However, we need to be cautious about translating a finding from mice to humans. Our research into that connection is ongoing."


Story Source:

The above story is based on materials provided by Georgetown University Medical Center. Note: Materials may be edited for content and length.


Journal Reference:

  1. Olga Catalina Rodriguez, Sujatra Choudhury, Vamsi Kolukula, Eveline E. Vietsch, Jason Catania, Anju Preet, Katherine Reynoso, Jill Bargonettti, Anton Wellstein, Chris Albanese and Maria Laura Avantaggiati. Dietary downregulation of mutant p53 levels via glucose restriction: Mechanisms and implications for tumor therapy. Cell Cycle, 2012

Cite This Page:

Georgetown University Medical Center. "Dietary glucose affects the levels of a powerful oncogene in mice." ScienceDaily. ScienceDaily, 15 November 2012. <www.sciencedaily.com/releases/2012/11/121115133152.htm>.
Georgetown University Medical Center. (2012, November 15). Dietary glucose affects the levels of a powerful oncogene in mice. ScienceDaily. Retrieved April 24, 2014 from www.sciencedaily.com/releases/2012/11/121115133152.htm
Georgetown University Medical Center. "Dietary glucose affects the levels of a powerful oncogene in mice." ScienceDaily. www.sciencedaily.com/releases/2012/11/121115133152.htm (accessed April 24, 2014).

Share This



More Plants & Animals News

Thursday, April 24, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Monkeys Are Better At Math Than We Thought, Study Shows

Monkeys Are Better At Math Than We Thought, Study Shows

Newsy (Apr. 23, 2014) A Harvard University study suggests monkeys can use symbols to perform basic math calculations. Video provided by Newsy
Powered by NewsLook.com
Raw: Leopard Bites Man in India

Raw: Leopard Bites Man in India

AP (Apr. 22, 2014) A leopard caused panic in the city of Chandrapur on Monday when it sprung from the roof of a house and charged at rescue workers. (April 22) Video provided by AP
Powered by NewsLook.com
Iowa College Finds Beauty in Bulldogs

Iowa College Finds Beauty in Bulldogs

AP (Apr. 22, 2014) Drake University hosts 35th annual Beautiful Bulldog Contest. (April 21) Video provided by AP
Powered by NewsLook.com
805-Pound Shark Caught Off The Coast Of Florida

805-Pound Shark Caught Off The Coast Of Florida

Newsy (Apr. 22, 2014) One Florida fisherman caught a 805-pound shark off the coast of Florida earlier this month. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins