Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Mol Cell Endocrinol. 2010 Sep 15;326(1-2):40-7. doi: 10.1016/j.mce.2010.02.040. Epub 2010 Mar 6.
Recently, progress has been made in understanding human pituitary tumor pathogenesis by the investigation of differences in gene expression between normal pituitary tissue and pituitary tumors. A number of approaches, including differential display (DD), representational difference analysis (RDA), and microarray analysis have been used and several molecular targets potentially associated with pituitary tumor development and invasion have been identified. We have used RDA to compare gene expression patterns between normal human pituitary and clinically non-functioning pituitary adenomas, and identified genes with growth suppression function which are expressed in the normal pituitary but not in pituitary tumors. In particular, we have focused on an imprinted gene, Maternally Expressed Gene 3 (MEG3), which is specifically associated with clinically non-functioning pituitary adenomas of a gonadotroph lineage. MEG3 functions to suppress tumor cell growth, increase protein expression of the tumor suppressor p53, and selectively activate p53 target genes. Interestingly, MEG3 does not encode a protein but a non-coding RNA. Therefore, these studies have revealed novel mechanisms for the function of a non-coding RNA in pituitary physiology and tumorigenesis.
最近，通过研究正常垂体组织和垂体肿瘤之间基因表达的差异，人们对人类垂体肿瘤发病机制的理解取得了进展。已经使用了包括差异显示（DD）、代表性差异分析（RDA）和微阵列分析在内的多种方法，并且已经确定了一些与垂体肿瘤发生和侵袭相关的潜在分子靶标。我们使用 RDA 比较了正常人类垂体和临床上无功能垂体腺瘤之间的基因表达模式，并且鉴定了在正常垂体中表达而不在垂体肿瘤中表达的具有生长抑制功能的基因。特别是，我们专注于印迹基因 Maternally Expressed Gene 3（MEG3），其与临床上无功能的促性腺激素谱系垂体腺瘤特异性相关。MEG3 的功能是抑制肿瘤细胞生长，增加肿瘤抑制因子 p53 的蛋白表达，并选择性地激活 p53 靶基因。有趣的是，MEG3 不编码蛋白质，而是编码非编码 RNA。因此，这些研究揭示了非编码 RNA 在垂体生理学和肿瘤发生中的功能的新机制。
