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Menin is a protein encoded by the gene mutated in multiple endocrine neoplasia type 1 (MEN1) characterized by multiple endocrine tumors of the parathyroid glands, pancreatic islets and the anterior pituitary, especially prolactinoma. In this study, we examined the effects of menin on human prolactin (hPRL) expression. In rat pituitary GH3 cells stably expressing menin, both PRL gene expression/secretion and thymidine incorporation into DNA were inhibited as compared with mock-transfected cells. The transcriptional activity of PRL promoter in GH3 cells co-transfected with menin was significantly decreased. A deletion mutation (569 delC), which we identified in a Japanese MEN1 family, was introduced into menin. When GH3 cells were transfected with a mutant menin expression vector, inhibition of hPRL promoter activity was partially reversed. These observations suggest that menin inhibits hPRL promoter activity and cell proliferation, raising the possibility that menin might play an important role in the tumorigenesis of prolactinoma.
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P. La, R. W. Schnepp, C. D. Petersen, A. C. Silva, and X. Hua Tumor Suppressor Menin Regulates Expression of Insulin-Like Growth Factor Binding Protein 2 Endocrinology, July 1, 2004; 145(7): 3443 - 3450. [Abstract] [Full Text] [PDF]
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 A. Lacerte, E.-H. Lee, R. Reynaud, L. Canaff, C. de Guise, D. Devost, S. Ali, G. N. Hendy, and J.-J. Lebrun Activin Inhibits Pituitary Prolactin Expression and Cell Growth through Smads, Pit-1 and Menin Mol. Endocrinol., June 1, 2004; 18(6): 1558 - 1569. [Abstract] [Full Text] [PDF]
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 H. Sowa, H. Kaji, R. Kitazawa, S. Kitazawa, T. Tsukamoto, S. Yano, T. Tsukada, L. Canaff, G. N. Hendy, T. Sugimoto, et al. Menin Inactivation Leads to Loss of Transforming Growth Factor {beta} Inhibition of Parathyroid Cell Proliferation and Parathyroid Hormone Secretion Cancer Res., March 15, 2004; 64(6): 2222 - 2228. [Abstract] [Full Text] [PDF]
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