A BTB/POZ protein, NAC-1, is related to tumor recurrence and is essential for tumor growth and survival

Kentaro Nakayama, Naomi Nakayama, Ben Davidson, Jim J.C. Sheu, Natini Jinawath, Antonio Santillan, Ritu Salani, Robert E. Bristow, Patrice J. Morin, Robert J. Kurman, Tian Li Wang, Ie Ming Shih*

*此作品的通信作者

研究成果: 期刊稿件文章同行評審

119 引文 斯高帕斯(Scopus)

摘要

Recent studies have suggested an oncogenic role of the BTB/POZ-domain genes in hematopoietic malignancy. The aim of this study is to identify and characterize BTB/POZ-domain genes in the development of human epithelial cancers, i.e., carcinomas. In this study, we focused on ovarian carcinoma and analyzed gene expression levels using the serial analysis of gene expression (SAGE) data in all 130 deduced BTB/POZ genes. Our analysis reveals that NAC-1 is significantly overexpressed in ovarian serous carcinomas and several other types of carcinomas. Immunohistochemistry studies in ovarian serous carcinomas demonstrate that NAC-1 is localized in discrete nuclear bodies (tentatively named NAC-1 bodies), and the levels of NAC-1 expression correlate with tumor recurrence. Furthermore, intense NAC-1 immunoreactivity in primary tumors predicts early recurrence in ovarian cancer. Both coimmunoprecipitation and double immunofluorescence staining demonstrate that NAC-1 molecules homooligomerize through the BTB/POZ domain. Induced expression of the NAC-1 mutant containing only the BTB/POZ domain disrupts NAC-1 bodies, prevents tumor formation, and promotes tumor cell apoptosis in established tumors in a mouse xenograft model. Overexpression of full-length NAC-1 enhanced tumorigenicity of ovarian surface epithelial cells and NIH 3T3 cells in athymic nu/nu mice. In summary, NAC-1 is a tumor recurrence-associated gene with oncogenic potential, and the interaction between BTB/POZ domains of NAC-1 proteins is critical to form the discrete NAC-1 nuclear bodies and essential for tumor cell proliferation and survival.

原文英語
頁(從 - 到)18739-18744
頁數6
期刊Proceedings of the National Academy of Sciences of the United States of America
103
發行號49
DOIs
出版狀態已出版 - 05 12 2006
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