Menin immunoreactivity in secretory granules of human pancreatic islet cells.
Menin immunoreactivity in secretory granules of human pancreatic islet cells.
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DOI：
10.1097/pai.0000000000000046
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发表时间：
2014-11
期刊：
影响因子：
--
通讯作者：
Emmert-Buck MR
中科院分区：
文献类型：
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作者：
Debelenko LV;Agarwal S;Du Q;Yan W;Erickson HS;Abu-Asab M;Raffeld MA;Libutti SK;Marx SJ;Emmert-Buck MR
The protein product of the Multiple Endocrine Neoplasia Type I (MEN1) gene is thought to be involved in predominantly nuclear functions; however, immunohistochemistry (IHC) data on cellular localization are conflicting. To further investigate menin expression, we analyzed human pancreas (an MEN1 target organ) using IHC and six antibodies raised against full-length menin or its peptides. In 10 normal pancreas specimens, two independently raised antibodies showed unexpected cytoplasmic immunoreactivity in peripheral cells in each islet examined (over 100 total across all 10 patients). The staining exhibited a distinct punctate pattern and subsequent immunoelectron microscopy indicated the target antigen was in secretory granules. Exocrine pancreas and pancreatic stroma were not immunoreactive. In MEN1 patients, unaffected islets stained similar to those in normal samples but with a more peripheral location of positive cells, whereas hyperplastic islets and tumorlets showed increased and diffuse cytoplasmic staining, respectively. Endocrine tumors from MEN1 patients were negative for menin, consistent with a two-hit loss of a tumor suppressor gene. Secretory granule localization of menin in a subset of islet cells suggests a function of the protein unique to a target organ of familial endocrine neoplasia, although the IHC data must be interpreted with some caution due to the possibility of antibody cross reaction. The identity, cellular trafficking, and role of this putative secretory granule-form of menin warrant additional investigation.
