期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2004
卷号：101
期号：29
页码：10833-10838
DOI：10.1073/pnas.0400690101
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Hedgehog signaling is suggested to be a major oncogenic pathway in medulloblastoma, which arises from aberrant development of cerebellar granule progenitors. Allelic loss of chromosome 17p has also been described as the most frequent genetic defect in this human neoplasia. This observation raises the question of a possible interplay between 17p deletion and the Hedgehog tumorigenic pathway. Here, we identify the human orthologue of mouse RENKCTD11, previously reported to be expressed in differentiating and low proliferating neuroblasts. Human RENKCTD11 maps to 17p13.2 and displays allelic deletion as well as significantly reduced expression in medulloblastoma. RENKCTD11 inhibits medulloblastoma cell proliferation and colony formation in vitro and suppresses xenograft tumor growth in vivo. RENKCTD11 seems to inhibit medulloblastoma growth by negatively regulating the Hedgehog pathway because it antagonizes the Gli-mediated transactivation of Hedgehog target genes, by affecting Gli1 nuclear transfer, and its growth inhibitory activity is impaired by Gli1 inactivation. Therefore, we identify RENKCTD11 as a suppressor of Hedgehog signaling and suggest that its inactivation might lead to a deregulation of the tumor-promoting Hedgehog pathway in medulloblastoma.
关键词：brain tumors ; tumor suppressor ; Gli ; 17p deletion
