Diagnosis of MEN1 in a patient with back pain

Diagnosis Of Multiple Endocrine Neoplasia Type 1 In A Patient With Back Pain; Case Report And Review Of Literature
-G Cristina, L Cesar A, L Robert, M Vinuta. Diagnosis Of Multiple Endocrine Neoplasia Type 1 In A Patient With Back Pain; Case Report And Review Of Literature. The Internet Journal of Internal Medicine. 2008 Volume 8 Number 1.

• "Usually MEN1 patients are first diagnosed when they present with hypercalcemia. Our patient’s diagnosis was made only after he presented with back and flank pain, and imaging of his abdomen incidentally noted multiple abdominal tumors."
  

Menin -today's growth promoter, tomorrow's tumor suppressor

Elucidating the Role of Menin During Islet Cell Development in the Human Fetal Pancreas
-Dubrick, Jessica L., (2013).  
University of Western Ontario - Electronic Thesis and Dissertation Repository. Paper 1287.
http://ir.lib.uwo.ca/etd/1287

editor's notes:

Menin functions as a tumor suppressor in adult endocrine cells, but in the fetal pancreas promotes cell survival and proliferation.  At first glance these roles seem very different, almost opposite.  But are they really opposed?

If menin promotes the proliferation of healthy pancreas cells -in particular, cells with at least one functional MEN1 gene- then it would seem that these cells will proliferate faster than those unable to produce menin.  So, cells that are unable to produce menin will represent a decreasing fraction of the cell population. Therefore, even during fetal development, menin's role as a growth promoter offers a tumor suppressive advantage to the developing pancreas, by reducing the percentage of cells that later may pose a tumorigenic risk due to their inability to express menin.

Unless I've got that wrong.

Link discovered between MEN1 and much-studied Hedgehog signal pathway

Menin Epigenetically Represses Hedgehog Signaling in MEN1 Tumor Syndrome
-Xianxin Hua, MD, PhD, Buddha Gurung, PhD, Perelman School of Medicine, University of Pennsylvania
Cancer Research April 15, 2013 73:2650-2658; Published OnlineFirst April 15, 2013;

Link discovered between MEN1 and much-studied cell pathway
A research team led by Xianxin Hua, MD, PhD, associate professor of Cancer Biology at the Abramson Family Cancer Research Institute, report in Cancer Research that menin suppresses signaling in the much-studied Hedgehog pathway in endocrine organs.

• "This study uncovered a new layer of regulation of pro-proliferative genes by menin via the Hedgehog signaling pathway," Hua says.
  
• "These pro-replication genes are regulated through GAS1 and PRMT5."
  
• The GAS1 protein promotes Hedgehog signaling.
  
• Menin interacts with the methylating enzyme PRMT5, and binds to the promoter of the Gas1 gene, inhibiting Gas1 gene transcription.
  
• By inhibiting Gas1 expression, menin and PRMT5 inhibit the pathway's tendency towards cell proliferation.
  
• Mutant menin proteins are impaired in their ability to interact with PRMT5, and lead to increased Hedgehog signaling and cell proliferation.
  
• Hua's team found that treating a mouse model of human MEN1 with a Hedgehog pathway inhibitor called Erivedge reduced proliferation of tumor cells and blood insulin levels. Hua says that this suggests a potential new treatment for MEN1 patients.
  

MEN Syndrome and M.E.N. 1: Parathyroid, Pituitary, Pancreas, Thyroid Tumors and MEN type 1 Syndrome - Disorders of the Parathyroid, Pituitary, and Pancreas

MEN Syndrome and M.E.N. 1: Parathyroid, Pituitary, Pancreas, Thyroid Tumors and MEN type 1 Syndrome - Disorders of the Parathyroid, Pituitary, and Pancreas

An overview of MEN1, its treatment, and what patients can expect.

By James Norman MD, FACS, FACE
Norman Parathyroid Center
http://www.parathyroid.com/Parathyroid-Surgeon.htm

What Extent of Pancreatic Resection Do Patients with MEN-1 Require?

What Extent of Pancreatic Resection Do Patients with MEN-1 Require?
-C. D. Adkisson, et al.
JOP. J Pancreas (Online) 2012 Jul 10; 13(4):402-408.

• "In patients with MEN-1 and pancreatic endocrine tumors, preoperative workup underestimates extent of disease and total pancreatectomy should be considered for complete tumor removal."
  

Asymptomatic children with multiple endocrine neoplasia type 1 (MEN1) mutations harbour pancreatic and pituitary tumours

Asymptomatic children with multiple endocrine neoplasia type 1 (MEN1) mutations harbour pancreatic and pituitary tumours
-Newey P, et al. Endocrine Abstracts (2009) 19 P171

• "...These two cases highlight the importance of screening children with MEN1 mutations as early diagnosis and treatment is likely to reduce both morbidity and mortality."

What is MEN1?

Multiple Endocrine Neoplasia Type 1 is a genetic disorder that greatly increases the risk of developing multiple cancerous and noncancerous tumors in glands such as the parathyroid, pituitary, and pancreas. These endocrine tumors may produce excessive levels of hormones that lead to secondary disease.

Individuals with MEN1 are born with one mutated copy of the MEN1 tumor suppressor gene in each cell. Cells that later develop a mutation in the remaining copy of the MEN1 gene then are left unable to produce menin, an important tumor suppressor protein. With no functional MEN1 gene, such cells may divide uncontrollably, resulting in the development of tumors.

MEN1 is also known as: MEN Type 1, MEN-1, Multiple Endocrine Adenomatosis Type 1, MEA Type 1, MEA 1, Wermer's syndrome.

references:
http://www.mayoclinic.org/men1/
http://en.wikipedia.org/wiki/Multiple_endocrine_neoplasia_type_1