Role of menin in neuroendocrine tumorigenesis.
The menin protein encoded by the MEN1 tumor suppressor gene is ubiquitously expressed and highly conserved evolutionarily. The combination of findings from current in vitro and in vivo studies has not yielded a comprehensive understanding of the mechanisms of menin's tumor suppressor activity or the specific role for menin in endocrine tumorigenesis, although its diverse interactions suggest possible pivotal roles in transcriptional regulation, DNA processing and repair and cytoskeletal integrity. This manuscript summarizes recent research findings including studies of global gene expression in MEN1-associated neuroendocrine tumors and pivotal changes in intracellular signaling pathways associated with neuroendocrine tumorigenesis. Finally, the clinical applications provided by the understanding of the effects of MEN1 gene mutations on neuroendocrine tumor development in patients with this familial cancer syndrome are discussed.
Lairmore
Terry C
TC
Division of Surgical Oncology, Scott and White Memorial Hospital Clinic, Texas A&M University System Health Sciences Center College of Medicine, 2401 S. 31st Street, Temple, Texas 76508, USA. tlairmore@swmail.sw.org
Chen
Herbert
H
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D007515:Islets of Langerhans / Q000166:cytology / Q000502:physiology; D008967:Molecular Biology; D018358:Neuroendocrine Tumors / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics / Q000378:metabolism; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D051792:Basic Helix-Loop-Helix Proteins; D011518:Proto-Oncogene Proteins; D019908:Proto-Oncogene Proteins c-raf; D051881:Receptor, Notch1; C065500:ASCL1 protein, human; C105373:MEN1 protein, human; C497761:NOTCH1 protein, human