Navigation Links
Key metabolic pathway implicated in intractable form of breast cancer
Date:7/18/2011

FINDINGS: Using a new in vivo screening system, Whitehead Institute researchers have identified a protein in a key metabolic pathway that is essential in estrogen receptor (ER)-negative breast cancer. When the expression of the gene that codes for this proteinphosphoglycerate dehydrogenase or PHGDHis suppressed in tumors and cell lines with an overabundance of the protein, the rate of cellular growth declines markedly.

RELEVANCE: PHGDH is overexpressed in approximately 70% of ER-negative breast cancer patients. Patients with ER-negative disease respond poorly to treatment and have a low five-year survival rate. In cells and tumors where it is overexpressed, PHGDH may represent a promising target for drug development.

CAMBRIDGE, Mass. (July 18, 2011) Using a new in vivo screening system, Whitehead Institute researchers have identified a protein in the serine biosynthesis pathway that is essential in estrogen receptor (ER)-negative breast cancera notoriously difficult disease to treat associated with low five-year survival rates.

According to the researchers, when expression of the gene that codes for this proteinphosphoglycerate dehydrogenase or PHGDHis suppressed in tumors and cell lines with an overabundance of the protein, the rate of cellular growth declines markedly.

As reported this month in Nature, the in vivo screen focused on 133 metabolic genes that the researchers predicted to be necessary for tumorigenesis. Using RNA interference (RNAi), first author Richard Possemato targeted these genes in human breast cancer cells implanted in mice.

"Our goal for this study was to look for essential cancer genes in vivo, where the levels of metabolites are likely more appropriate than in an in vitro model system," says Possemato, a postdoctoral researcher in the lab of Whitehead Member David Sabatini.

In vivo screening provides a more realistic understanding of what would work in a living organism rather than in a Petri dish's artificial environment. During the screen Possemato and colleagues identified PHGDH, which is overexpressed in approximately 70% of ER-negative breast cancer patients, as essential to tumor growth. The PHGDH protein is one of three enzymes involved in the metabolic serine biosynthesis pathway. Cancer cells alter their metabolism in the interest of sustaining rapid growth, and high levels of PHGDH appear to drive such metabolic change. When Possemato suppressed PHGDH protein production in breast cancer cell lines with elevated levels of it, the cells stopped proliferating.

The findings suggest that PHGDH may represent a promising target for drug development for ER-negative breast cancer.

"We do think this has some therapeutic relevance, where an inhibitors of this enzyme would have effects on the cells we identified that tend to overexpress this enzyme," says Sabatini, who is also a biology professor at MIT. "By RNAi, we've provided proof of principle, but whether a drug against this protein would be valuable remains to be determined."


'/>"/>

Contact: Nicole Giese
giese@wi.mit.edu
617-258-6851
Whitehead Institute for Biomedical Research
Source:Eurekalert

Related biology news :

1. Hold your breath: Air pollution plays role in cardiac, metabolic diseases
2. Study shows pine bark naturally improves kidney function in patients with metabolic syndrome
3. Metabolic cost of human sleep deprivation quantified by University of Colorado team
4. Birch bark ingredient comes with many metabolic benefits
5. Seaweed as biofuel? Metabolic engineering makes it a viable option
6. Longevity breakthrough: The metabolic state of mitochondria controls life span
7. Study finds low vitamin-d levels in northern California residents with metabolic syndrome
8. AgriLife scientist: Functional amino acids regulate key metabolic pathways
9. Imaging reveals key metabolic factors of cannibalistic bacteria
10. Native-like spider silk produced in metabolically engineered bacterium
11. Researchers discover metabolic vulnerability in TB and potential drug target
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/2/2017)...  Central to its deep commitment to honor ... Japan Prize Foundation today announced the laureates of ... envelope in their respective fields of Life Sciences ... being recognized with the 2017 Japan Prize for ... to the advancement of science and technology, but ...
(Date:1/31/2017)... Jan. 31, 2017  Spero Therapeutics, LLC, a ... the treatment of bacterial infections, today announced it ... candidates from Pro Bono Bio Ltd (PBB) to ... multi-drug resistant forms of Gram-negative bacteria.   The assets ... Ltd, a PBB group company. "The ...
(Date:1/26/2017)... 2017  Crossmatch, a leading provider of security and ... at combatting fraud, waste and abuse in assistance operations ... Action on Disaster Relief conference in Panama ... agencies and foreign assistance organizations throughout Latin ... are a largely unacknowledged problem in the foreign assistance ...
Breaking Biology News(10 mins):
(Date:2/22/2017)... DES MOINES, Iowa , Feb. 22, 2017 Origin ... an agricultural biotechnology trait and seed provider, and Arcadia ... -based company that develops and commercializes agricultural productivity traits and ... of a key corn biotechnology product developed in China ... completion of global regulatory trials. ...
(Date:2/22/2017)... PHOENIX and SAN DIEGO ... Technology Holdings (the "Company") (OTCQB:CELZ) announced today expansion ... universal donor stem cell product through establishment of ... initiated research activities at the San Diego BioLabs ... Companies, Boehringer Ingelheim, Novartis, and Sanofi. ...
(Date:2/21/2017)... ... February 21, 2017 , ... During HIMSS 2017, CloudMine, ... applications, announced a partnership with Redox, a leader in cloud-based healthcare integration and ... systems while keeping data secure in the cloud. , The digital health developers, ...
(Date:2/21/2017)... (PRWEB) , ... February 21, 2017 , ... The medical ... for their use, in multiple areas of medicine, due to their differentiating characteristics. Stem ... and they have the ability to be induced to become tissue or organic-specific cells ...
Breaking Biology Technology: