NEW YORK (Reuters Health) - Scientists from Canada report that the DJ-1 gene, located in the PARK7 locus of chromosome 1p36, likely plays a role in human carcinogenesis by interfering with the well-known tumor suppressor gene PTEN.
DJ-1 may be a useful prognostic marker for cancer and is “an amazing drug target for the development of cancer drugs,” Dr. Tak W. Mak from the Ontario Cancer Institute in Toronto said in a telephone interview with Reuters Health.
In the March issue of Cancer Cell, he and his colleagues note that PTEN antagonizes the PI3 kinase and PKB/Akt signaling pathways, which regulate cell growth and survival. But what regulates PTEN is unclear.
“Our results strongly suggest that DJ-1 straight-jackets PTEN and prevents it from working,” Dr. Mak said.
In mammalian cells, underexpression of DJ-1 correlates with decreased PKB/Akt activity, while overexpression leads to increased activity and increased cell survival.
In primary breast cancer cells, elevated DJ-1 levels correlate with elevated PKB/Akt activity and reduced PTEN expression. In primary non-small cell lung cancer cell samples, DJ-1 expression was increased compared with healthy lung tissue and was associated strongly with poor prognosis.
In their studies, the 3-year risk of relapse for lung cancer patients with high DJ-1 expression in tumors was 46% versus 28% for patients with low DJ-1 tumor expression, Dr. Mak said. DJ-1’s effects were greatest for early stage I lung tumors where the incidence of relapse was 45% for patients with high levels of DJ-1 compared with 18% for those with low levels of DJ-1.
“We think DJ-1 overexpression drives lung cancer and presumably other cancers as well because it is linked to PTEN,” Dr. Mak said.
Loss of DJ-1 function may also play a role in neurodegeneration. Recently, a European team identified mutations in the DJ-1 gene in two separate families affected by early-onset Parkinson’s disease. (See Reuters Health report, November 21, 2002)
Taken together, the data suggest that “both gain and loss of function of DJ-1 has a major impact on health,” Dr. Mak said, “so when you have loss of function of DJ-1, you get Parkinson’s and when you have gain of function of DJ-1 you get cancer.”
Source: Cancer Cell 2005;7:263-273. [ Google search on this article ]
MeSH Headings:Biological Sciences: Biology: Gene Expression Regulation: Genetics: Genetics, Biochemical: Lung Neoplasms: Molecular Biology: Neoplasms: Neoplasms by Site: Respiratory Tract Neoplasms: Thoracic Neoplasms: Gene Expression Regulation, Neoplastic: Biological Sciences: DiseasesCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
