New insight into aggressive childhood cancer

Jan 05, 2009

A new study reveals critical molecular mechanisms associated with the development and progression of human neuroblastoma, the most common cancer in young children. The research, published by Cell Press in the January 6th issue of the journal Cancer Cell, may lead to development of future strategies for treatment of this aggressive and unpredictable cancer.

Neuroblastoma cells are derived from migratory neural crest cells that give rise to the peripheral sympathetic nervous system. During normal development, neural crest cells stop dividing and differentiate. However, neuroblastoma cells seem to have lost this capacity. Previous work has shown that amplification of the MYCN gene, which disrupts control of cell division and differentiation, is a strong predictor of poor prognosis in neuroblastoma.

"We speculated that genes that are expressed in a MYCN-dependent manner might be required specifically for the growth of MYCN-amplified neuroblastomas and that MYCN-amplified neuroblastomas might depend not only on N-Myc itself, but also on upstream regulatory factors or downstream target genes," explains senior study author, Dr. Martin Eilers, from the University of Wurzburg in Germany.

Dr. Eilers and colleagues performed a genetic screen of nearly 200 genes that are dependent on amplified MYCN in human neuroblastoma or are direct targets of Myc. The researchers found that the oncogene AURKA is required for growth of MYCN-amplified neuroblastoma cells, but not cells lacking amplified MYCN.

AURKA encodes the kinase Aurora A which is dysregulated in multiple types of cancer cells. Interestingly, Aurora A kinase activity was not required for N-Myc stabilization. Instead, elevated Aurora A levels in MYCN-amplified neuroblastoma cells interfered with the PI3-kinase-dependent and mitosis-specific degradation of N-Myc. This suggests that small molecule inhibitors of Aurora A kinase may not be effective at inhibiting the oncogenic functions of Aurora A.

"Our results show that stabilization of N-Myc is a critical oncogenic function of Aurora A in childhood neuroblastoma; the challenge will now be to find ways to interfere with this function in order to find new approaches for the therapy of these tumors," says Dr. Eilers. "The findings also suggest that the current views about why Aurora A is oncogenic may need to be re-evaluated."

Source: Cell Press

Explore further: Researchers find chemotherapy after bladder cancer surgery improved survival

add to favorites email to friend print save as pdf

Related Stories

Korean tech start-ups offer life beyond Samsung

20 hours ago

As an engineering major at Seoul's Yonsei University, Yoon Ja-Young was perfectly poised to follow the secure, lucrative and socially prized career path long-favoured by South Korea's elite graduates.

NASA satellite sees a warm winter in the Western US

6 hours ago

While people in the eastern two-thirds of the U.S have been dealing with Arctic Air, the bulge in the Jet Stream over the eastern Pacific Ocean has been keeping the western third of the U.S. in warmer than ...

Recommended for you

Deodorant use ok for radiotherapy patients

Feb 27, 2015

Women undergoing radiotherapy for breast cancer can use deodorant without fear of increased underarm skin reaction, pain, itching or burning, research suggests.

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.