When we think about merlin (the NF2 gene protein), we probably think first about the brain and nerves where merlin protein regulates normal cell growth. When merlin protein doesn’t work properly, which is the case in individuals with NF2, vestibular schwannomas and the other nerve tumors associated with NF2 might grow, due to increased amounts of cell division. Now a new study* reveals that merlin also plays an important role in activating and regulating cell growth … in the liver. The NF2 gene which encodes merlin protein was specifically deleted from liver cells in a genetically engineered mouse model, and this led to an immediate overgrowth of progenitor (stem-like) cells in the liver. This happened whether merlin gene was deleted in the developing mouse, or in the adult mouse. The mice that survived this burst of cell growth went on to develop cholangiocellular and hepatocellular carcinoma – types of liver tumor. This liver cell growth in the absence of merlin protein seems to be driven by hyperactive signaling in the epidermal growth factor receptor (EFR) as the increased growth of liver cells could be blocked by treating the mice with anti-EGFR drug.
The study is headed by Dr. Andi McClatchey (Massachusett General Hospital) and authors also include Dr. Marco Giovannini (House Ear Institute). Both are NF2 site directors from the Children’s Tumor Foundation NF Preclinical Consortium. This research points toward a brand new role for merlin protein in regulating normal liver development and growth. Given the dramatic amount of liver cell growth and drug response reported, these mice may also be very helpful for initial testing of drugs intended as candidates for treatment of NF2 vestibular schwannomas and other nerve tumors.
* Benhamouche S, Curto M, Saotome I, Gladden AB, Liu CH, Giovannini M, McClatchey AI. (2010) Nf2/Merlin controls progenitor homeostasis and tumorigenesis in the liver. Genes Dev. 2010 Jul 30. [Epub ahead of print]
