Content area
Full Text
About the Authors:
Seung-Beom Hong
Affiliation: Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, United States of America
HyoungBin Oh
Affiliation: Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, United States of America
Vladimir A. Valera
Affiliation: Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, United States of America
Masaya Baba
Affiliation: Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, United States of America
Laura S. Schmidt
Affiliations Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, United States of America, Basic Science Program, SAIC-Frederick, Inc., National Cancer Institute at Frederick, Frederick, Maryland, United States of America
W. Marston Linehan
* E-mail: [email protected]
Affiliation: Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, United States of America
Introduction
Genetic studies have revealed several tumor suppressor genes [von hippel lindau (VHL), fumarate hydratase (FH), succinate dehydrogenase subunit B (SDHB) and folliculin (FLCN)] and proto-oncogenes (hepatocyte growth factor receptor MET) that are responsible for the development of renal cell carcinoma (RCC) [1]. In addition, two groups of transcription factors have been implicated in the development of RCC. Hypoxia-inducible factors (HIFs) were originally reported to be stabilized by the inactivation of the VHL tumor suppressor gene [2]. HIF stabilization is also correlated with mutations in FH or SDHB and is important in tumor cell growth and angiogenesis [3], [4]. TFE3 and TFEB, members of the MiTF/TFE transcription factor family, are highly expressed in the nucleus as a result of chromosomal translocations and are responsible for the development of juvenile renal cancer [5], [6]. However, the dysregulation of TFE3 or TFEB as a consequence of mutations in other tumor suppressor genes has not been reported. Here we investigated the regulation of TFE3 activity by the FLCN tumor suppressor gene.
Translocation renal cell carcinomas (RCCs) are rare tumors mainly reported in children and young adults [7]. They are classified as a distinct subtype and are characterized by various translocations that frequently involve TFE3 and, infrequently, TFEB. Both TFE3 and TFEB harbor basic helix-loop-helix-leucine zipper (bHLH-LZ) DNA binding domains and belong to the MiTF/TFE transcription factor subfamily, which also include microphthalmia transcription factor (MiTF) and transcription factor EC (TFEC)...