垂体瘤基因表达谱的建立及其发病分子机理的探讨

Study on the Gene Expression Profile and Molecular Mechanism of Pituitary Tumors

目的 建立垂体瘤组织基因表达谱并探讨其发病的分子机理。方法垂体生长激素瘤（ＧＨＰＡ）和无功能腺瘤（ＮＦＰＴ）ｃＤＮＡ文库构建，大规模表达序列标签（ｅｘｐｒｅｓｓｅｄ ｓｅｑｕｅｎｃｅ ｔａｇｓ，ＥＳＴｓ）测序及生物信息学处理。结果 在已知基因中，参与基因蛋白表达者最高（分别为２９％和２８％），其次是代谢相关基因（分别为１８％和２１％），均较正常垂体为高（２３．２％和１４．３％）。ＧＨＰＡ中可同时表达泌乳素（ＰＲＬ）和生长激素（ＧＨ）；ＧＨＰＡ和正常垂体（ＮＰ）中ＧＳａ基因表达明显高于钙调素，而ＮＦＰＴ中则相反。在垂体瘤差异表达的与细胞分裂有关的基因中，有些与肿瘤的发生有关；发现了７４个在垂体瘤中高表达而正常垂体中不表达的未知基因的ＥＳＴｓ。结论 不同垂体瘤组织中其主要的信号转导途径可能有别；发现有些与细胞分裂有关的基因在ＮＦＰＴ或ＧＨＰＡ库中与ＮＰ库中表达不同。

Objective To study the gene expression profile and molecular mechamism of pituitary tumors. Methods cDNA libraries of the non functional pituitary tumor (NFPT) and GH -- producing adenoma (GHPA) were constructed. Large -- scale sequencing and bioinformatics were used. Results 1253 and 603 ESTs of good quality were produced from NFPT and GHPA cDNA libraries respectively. The categories of genes most highly expressed in these pituitary tumors were those participating in gene/protein expression (29% and 28% from NFPT and GHPA respectively), and the next were those related with metabolism (18% and 21% from NFPT and GHPA, respectively). Compared with ESTs data from the normal pituitary, the expressions of these two categories of genes were higher in pituitary tumors. The FSH β subunit gene is expressed in NFPT, while the GH and PRL gene in GHPA. Comparing the gene expression profiles of these libraries, we found that the expression of GSa gene was higher than that of calmodulin in GH -- producing adenoma and the normal pituitary, but the reverse occurred in the non functional pituitary tumor. By electronic hybridization, we found some genes in the category related with cell division, which were expressed in the pituitary tumor, but not in the normal pituitary, and some of those were found to be involved in tumorigenesis. 74 ESTs representing new genes were only expressed in the pituitary tumor but not in the normal pituitary. Conclusion The gene expression profile study suggested that the metabolism and the gene/protein expression are more active in pituitary tumors than in the normal pituitary. The main signal transduction pathway may be different in various pituitary tumors. By comparing three libraries, it was found that the expression of some genes involved in cell division is different in NFPT or GHPA from that in the normal pituitary.