Involvement of the MEN1 Gene in Hormone-Related Cancers: Clues from Molecular Studies, Mouse Models, and Patient Investigations

Abstract

MEN1 mutation predisposes patients to multiple endocrine neoplasia type 1 (MEN1), a genetic syndrome associated with the predominant co-occurrence of endocrine tumors. Intriguingly, recent evidence has suggested that MEN1 could also be involved in the development of breast and prostate cancers, two major hormone-related cancers. The first clues as to its possible role arose from the identification of the physical and functional interactions between the menin protein, encoded by MEN1, and estrogen receptor α and androgen receptor. In parallel, our team observed that aged heterozygous Men1 mutant mice developed cancerous lesions in mammary glands of female and in the prostate of male mutant mice at low frequencies, in addition to endocrine tumors. Finally, observations made both in MEN1 patients and in sporadic breast and prostate cancers further confirmed the role played by menin in these two cancers. In this review, we present the currently available data concerning the complex and multifaceted involvement of MEN1 in these two types of hormone-dependent cancers.