Laboratory of Molecular Biology and Immunology, Department of Pharmacy, School of Health Sciences, University of Patras, 26500 Rio, Greece.
Best Pract Res Clin Endocrinol Metab. 2010 Jun;24(3):425-37. doi: 10.1016/j.beem.2010.01.001.
Cyclin-dependent kinase inhibitors (CDKIs) are known targets to become deregulated in various tumour types, including endocrine tumours. Typically, these cell cycle regulators are somatically inactivated in sporadic endocrine tumours. Recently, it became known that certain CDKI genes cause inherited susceptibility to endocrine neoplasia. Multiple endocrine neoplasia type 4 (MEN4) emerged as a novel form of multiple endocrine neoplasia, caused by mutations in the CDKI gene CDKN1B/p27(Kip1). The MEN4 phenotype remains unclear, but all MEN4 patients identified thus far present with parathyroid involvement, and less typically with pituitary adenomas and other endocrine features. Moreover, the CDKI gene CDKN2C/p18(INK4C) has been also implicated in endocrine neoplasia susceptibility. This review presents the recent advances in these novel MEN-related states and summarises the current knowledge of how these CDKIs may be implicated in endocrine neoplasia. In addition, it briefly presents data from Cdkn1b/p27(Kip1) and Cdkn2c/p18(INK4C) murine models, which strongly support the protective role of these inhibitors against endocrine tumourigenesis.
细胞周期蛋白依赖性激酶抑制剂 (CDKIs) 是各种肿瘤类型中失调的已知靶点，包括内分泌肿瘤。通常，这些细胞周期调节剂在散发性内分泌肿瘤中会发生体细胞失活。最近，人们发现某些 CDKI 基因导致内分泌肿瘤的遗传性易感性。多发性内分泌瘤 4 型 (MEN4) 是一种新型多发性内分泌瘤，由 CDKI 基因 CDKN1B/p27(Kip1) 的突变引起。MEN4 表型尚不清楚，但迄今为止所有鉴定的 MEN4 患者均存在甲状旁腺受累，且垂体腺瘤和其他内分泌特征不那么常见。此外，CDKI 基因 CDKN2C/p18(INK4C) 也与内分泌肿瘤易感性有关。本文介绍了这些与 MEN 相关的新状态的最新进展，并总结了目前关于这些 CDKIs 如何参与内分泌肿瘤发生的知识。此外，它还简要介绍了 Cdkn1b/p27(Kip1) 和 Cdkn2c/p18(INK4C) 小鼠模型的数据，这些数据强烈支持这些抑制剂对内分泌肿瘤发生的保护作用。
