垂体生长激素（GH）腺瘤发生于垂体前叶，位于激素分泌的中轴线上。在基础临床研究中分为内分泌和一般肿瘤生物学行为（增殖、侵袭）两个方向。交叉领域研究的欠缺限制了人们对这一特殊内分泌肿瘤发病机制的充分认识。如何兼顾抑制肿瘤生长和有效降低GH水平成为当前面临的首要难题。项目拟针对此状况，从腺瘤细胞调控GH分泌的GHRH和GHSR信号通路入手，研究通路间存在的协同和交叉反馈作用，探索其在内分泌调节、增殖、侵袭作用间的相互联系。重点研究PKCσ、B-Raf和其特有的gsp突变在上述环节中的相互关系；阐明PKCσ在介导GH分泌、增殖、侵袭信号通路间的联结作用和突出地位，B-Raf对ERK的调节作用及gsp突变对PKCσ、B-Raf作用的影响；深入探索它们在GH腺瘤中的作用机制。并凭借我们在该肿瘤研究中的优势，结合临床实际，证实上述关键基因、蛋白在判断GH腺瘤预后、生长抑素药物耐药中的作用。

With the capacity of over secreting growth hormone, originated from the front lobe of pituitary gland, somatotropic adenoma, prefers to recurrence after surgical resection and medical therapy. It has been separated into two independent fields in fundamental and clinic researches, based on its two features. One of its two remarkable characters is endocrinal character, such as GHRH-controlled or self-conrolled hormone producing while the other is the general biological character of neoplasia, such as proliferation and invasion. To a certain extent, the separaction has restricted the comprehensive recognition and further research development of somatotrophic adenoma, and caused these two fields falling into an embarrassing position. For its special tumor initiating mechanism, interdiscipline of the two different characters, is nearly absent. Integrated researches and interdiscipline of the two fields are necessary for this special tumor. They are useful for us to find some methods to both inhibit tumor overgrowth and effectively decrease GH level right. As for this condition, the project would start with cell signaling pathway of GHRH and GHSR that regulates the GH secretion in somatotrophic adenoma, paying attention to the cooperative and feedback function and investigating their interaction between endocrinal regulation, proliferation and invasion. Based on above link, we will examine the relationships among PKCσ,B-Raf and the typical gsp mutation of the somatotrophic adenoma. It would be clarified the prominent position of PKCσ in regulating cell signaling pathway mediating GH secretion, proliferation and invasion. Also, the positive regulatory role for B-Raf in MEK-ERK and the impact of gsp mutation engaged in PKCσ and B-Raf will be investigated to explore their regulation in cell signaling mediating growth hormone secreting,cell proliferation and cell invasion of somatotropic adenoma in this project. Finally, with the superiority of our work on somatotropic adenoma, combined with clinical practice, we'd confirm that the key gene and enzymes(gsp,PKCσ and B-Raf) play a important role in judging prognosis and drug resistance of somatotropic adenoma.