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:4/11/2017)... DUBLIN , Apr. 11, 2017 Research ... Tracking Market 2017-2021" report to their offering. ... The global eye tracking market to grow at ... The report, Global Eye Tracking Market 2017-2021, has been prepared based ... report covers the market landscape and its growth prospects over the ...
(Date:4/5/2017)... 2017 Today HYPR Corp. , leading ... component of the HYPR platform is officially FIDO® ... security architecture that empowers biometric authentication across Fortune 500 ... secured over 15 million users across the financial services ... home product suites and physical access represent a growing ...
(Date:3/30/2017)... March 30, 2017 The research team of ... three-dimensional (3D) fingerprint identification by adopting ground breaking 3D fingerprint minutiae ... realm of speed and accuracy for use in identification, crime investigation, ... cost. ... A research ...
Breaking Biology News(10 mins):
(Date:9/15/2017)... ... September 15, 2017 , ... San Diego based ... ‘Internal Seed B’ round of financing, totaling $600,000. The round was entirely ... ‘SAFE’ documentation structure at a company valuation of $10M. , Grolltex, ...
(Date:9/14/2017)... ... September 14, 2017 , ... ... (CC) product portfolio, clinically-relevant starting and ancillary materials that generate unprecedented efficiencies ... Cell (hMSC)-based therapies. The CliniControl product portfolio will radically simplify major steps ...
(Date:9/14/2017)... ... September 14, 2017 , ... One of the world’s largest World ... , For six hours that day, the GenCure Marrow Donor Program will be signing ... H-E-B grocery stores in San Antonio. , The registration tables will be staffed by ...
(Date:9/13/2017)... ... September 13, 2017 , ... ... life sciences industry to improve patient outcomes and quality of life for more ... has been named a US expert to the International Standards Organization/Technical Committee ...
Breaking Biology Technology: