'Notch'ing up a role in the multisystem disease tuberous sclerosis complex

December 28, 2009

Two independent teams of researchers have identified a role for enhanced activation of the signaling protein Notch in tumors characterized by inactivation of either the TSC1 or the TSC2 protein. As indicated by Warren Pear, at the University of Pennsylvania, Philadelphia, in an accompanying commentary, these data provide a rationale for testing whether Notch inhibitors are of benefit to those with TSC-associated tumors.

Tuberous sclerosis complex (TSC) is a multisystem disease characterized by the formation of benign tumors in multiple organs. It is caused by mutations in either the TSC1 or TSC2 gene. In the first study, Elizabeth Petri Henske, at Brigham and Women's Hospital, Boston, and Fabrice Roegiers, at Fox Chase Cancer Center, Philadelphia, found evidence of Notch signaling pathway activation in human angiomyolipomas, benign kidney tumors often found in patients with TSC, and in an angiomyolipoma-derived cell line. Importantly, inhibition of Notch suppressed proliferation of TSC2-deficient rat cells in a xenograft model. These authors therefore conclude that TSC proteins regulate Notch activity and that Notch dysregulation may underlie some of the distinctive clinical and pathologic features of TSC.

Results presented in the second study, by Hongbing Zhang and colleagues, at the Chinese Academy of Medical Sciences and Peking Union Medical College, People's Republic of China, provide further evidence that TSC proteins regulate Notch activity and that Notch overactivity contributes to the tumorigenic potential of cells deficient in either TSC1 or TSC2.
-end-
TITLE: The evolutionarily conserved TSC/Rheb pathway activates Notch in tuberous sclerosis complex and Drosophila external sensory organ development

AUTHOR CONTACT:
Elizabeth Petri Henske
Brigham and Women's Hospital, Boston, Massachusetts, USA.
Phone: (617) 355-9049; Fax: (617) 355-9016; E-mail: Ehenske@partners.org.

Fabrice Roegiers
Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
Phone: (215) 728-5518; Fax: (215) 214-2412; E-mail: Fabrice.Roegiers@fccc.edu.

View this article at: http://www.jci.org/articles/view/40221?key=76V59G6WkmwhlzpC43Dd

ACCOMPANYING ARTICLE
TITLE: Mammalian target of rapamycin regulates murine and human cell differentiation through STAT3/p63/Jagged/Notch cascade

AUTHOR CONTACT:
Hongbing Zhang
Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
Phone: 01186-10-65296495; Fax: 01186-10-65296491; E-mail: hbzhang2006@gmail.com or hbzhang@ibms.pumc.edu.cn.

View this article at: http://www.jci.org/articles/view/37964?key=tW45bTOVxrubVqRN67Lq

ACCOMPANYING COMMENTARY
TITLE: New roles for Notch in tuberous sclerosis

AUTHOR CONTACT:
Warren S. Pear
University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Phone: (215) 573-7764; Fax: (215) 573-6875; E-mail: wpear@mail.med.upenn.edu.

View this article at: http://www.jci.org/articles/view/41897?key=4b97bbae87d939f277f7

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