JCI online early table of contents: April 8, 2008

EDITOR'S PICK

Too many gene copies stimulate tumor cell growth

New data, generated by Peter Lichter and colleagues, at the German Cancer Research Center, Heidelberg, have characterized a molecular pathway underlying low-grade forms of a type of brain tumor known as an astrocytoma. The authors therefore suggest that therapeutics targeting this pathway might provide a new approach to treating individuals with low-grade atrocytomas.

Analysis of the DNA of astrocytomas from a large number of children revealed that the most common genetic mutation was the duplication of a region of DNA containing the BRAF gene. Tumors with this genetic mutation showed signs of increased BRAF protein activity. Consistent with the idea that increased BRAF activity had a role in the development of the tumors, mutations in the BRAF gene that caused increased BRAF protein activity were detected in tumors that did not exhibit duplication of the region of DNA containing the BRAF gene. As pharmacologic and genetic silencing of the BRAF signaling pathway and the BRAF gene, respectively, prevented tumor cells from low-grade gliomas growing in culture, it was suggested that inhibiting the signaling pathway downstream of BRAF might be beneficial for individuals with low-grade atrocytomas.

TITLE: BRAF gene duplication constitutes a mechanism of MAPK pathway activation in low-grade astrocytomas

AUTHOR CONTACT:

Peter Lichter

German Cancer Research Center, Heidelberg, Germany.

Phone: 49-6221-424619; Fax: 49-6221-424639; E-mail: .

View the PDF of this article at: https://www.the-jci.org/article.php?id=33656

EDITOR'S PICK

Small molecule miRNAs regulate female mouse fertility

Small molecules known as miRNAs, which are generated naturally by the body, regulate the conversion of genetic information into proteins. New data, generated by Jiahuai Han and colleagues, at The Scripps Research Institute, La Jolla, have now indicated that miRNAs can control the fertility of female mice.

The generation of miRNAs is a complex process that involves a protein known as Dicer. In the study, mice expressing substantially lower levels of Dicer than normal mice (Dicerd/d mice) were found to have only one defect — the female mice were infertile. Infertility was a result of impaired functioning of the corpus luteum, the structure that forms at the site of release of the fertilized egg and that is required to maintain pregnancy at the early stages. Detailed analysis indicated that the functioning of the corpus luteum was impaired because it was unable to form new blood vessels, and that this was associated with increased expression of the protein TIMP1, which inhibits blood vessel formation. As injection of the miRNAs miR17-5p and let7b into the ovaries of Dicerd/d mice decreased expression of TIMP1 and increased the number of blood vessels in the corpus luteum, the authors concluded that the development and function of the corpus luteum in mice is tightly regulated by miRNAs.

TITLE: Impaired microRNA processing causes corpus luteum insufficiency and infertility in mice

AUTHOR CONTACT: