The relationship between the expression of Pituitary Adenylate Cyclase-Activating Polypeptide & its receptors and apoptosis in human pituitary adenomas

垂体腺苷酸环化酶激活多肽与表达的关系

• 批准号: 13671462
• 负责人: OKA Hidehiro
• 金额: $ 1.02万
• 依托单位: Kitasato University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671462/
• 关键词: pituitary adenoma; apoptosis; PACAP; PVR; p16; p21; p27; p53; pituitary adenoma; apoptosis; receptor; PVR mRNA; CDK; Pituitary adenoma; Hormone receptor; mRNA; apeptosis

Pituitary adenylate cyclase-activating polypeptide (PACAP) was originally isolated from hypothalamic tissue based on its ability to stimulate cAMP production in cultured anterior pituitary cells. Recent studies have suggested a functional role for PACAP in the apoptosis of brain cells. However, the role of PACAP in regulating apoptosis in human pituitary adenomas has not previously been examined. Analysis of the cultured human pituitary adenoma cell line HP75 and human pituitary adenomas, which expresses all three major PACAP receptors, showed that both PACAP-38 and PACAP-27 inhibited TGF-s1-induced apoptosis. Treatment with the PACAP receptor antagonists PACAP 6?38 (PACAP type I receptor antagonist) and (p-chloro-D-Phe6, Leu17)-VIP (PACAP type II receptor antagonist) blocked the effects of PACAP-38 on the inhibition of transforming growth factor-s1 (TGF-s1)-induced apoptosis, confirming the specificity of the role of PACAP. Immunocytochemical analysis of the cell cycle cyclin-dependent kinase inhibitor p16, p21, p27 showed only p27 expression in human pituitary adenomas. These results indicate that PACAP is a highly specific inhibitor of TGF-s1-induced apoptosis in the HP75 human pituitary adenoma cell line. Pituitary adenomas expressed p16, p21, p27 and p53 mRNAs by real time RT-PCR. However, in protein level, only p27 expressed in human pituitary adenomas. Moreover, cyclin D3 as oncogene highly expressed in human pituitary adenomas but not cyclin B1 or D1.

垂体腺苷酸环化酶激活多肽（PACAP）最初是基于其刺激培养的垂体前叶细胞产生cAMP的能力而从下丘脑组织中分离的。最近的研究表明，PACAP在脑细胞凋亡中的功能作用。然而，PACAP在调节人垂体腺瘤细胞凋亡中的作用以前没有被研究过。对培养的人垂体腺瘤细胞系HP 75和表达所有三种主要PACAP受体的人垂体腺瘤的分析表明，PACAP-38和PACAP-27均抑制TGF-β 1诱导的细胞凋亡。治疗与PACAP受体拮抗剂PACAP 6？PACAP-38（PACAP I型受体拮抗剂）和（p-chloro-D-Phe 6，Leu 17）-VIP（PACAP II型受体拮抗剂）阻断了PACAP-38对转化生长因子-s1（TGF-s1）诱导的细胞凋亡的抑制作用，证实了PACAP作用的特异性。细胞周期蛋白依赖性激酶抑制剂p16、p21、p27的免疫细胞化学分析显示，在人垂体腺瘤中仅p27表达。这些结果表明，PACAP是一个高度特异性的抑制剂TGF-β 1诱导的HP 75人垂体腺瘤细胞系的凋亡。真实的RT-PCR检测p16、p21、p27和p53基因mRNA的表达。而在蛋白水平上，垂体腺瘤中仅p27表达。此外，cyclin D3作为癌基因在垂体腺瘤中高表达，而cyclin B1和D1则不表达。

项目成果

Utsuki S, Oka H, et al.: "Long-term outcome of intracranial germinoma with hCG elevation in cerebrospinal fluid but not in serum"Acta Neurochir(Wien). 144. 1151-1155 (2002)

Utsuki S、Oka H 等人：“颅内生殖细胞瘤的长期结果，脑脊液中 hCG 升高，但血清中不升高”Acta Neurochir (Wien)。

Hong-Lei Wang, Hidehiro Oka, Zheng Kang, Kiyotaka Fujii: "Anatomical study of the endoscopic transnasal transsphenoidal approach for pituitary surgery"Kitasato Med. 31. 227-231 (2001)

Hong-Lei Wang、Hidehiro Oka、Zheng Kang、Kiyotaka Fujii：“垂体手术内镜经鼻蝶入路的解剖学研究”Kitasato Med。

Suzuki S, Oka H, Kawano N, Tanaka S, Utsuki S, Fujii K: "Prognostic value of Ki-67 (MIB-1) and p53 in ependymomas."Brain Tumor Pathol. 18. 151-154 (2001)

Suzuki S、Oka H、Kawano N、Tanaka S、Utsuki S、Fujii K：“Ki-67 (MIB-1) 和 p53 在室管膜瘤中的预后价值。”脑肿瘤病理学。

Satoshi Utsuki, Yuichi Sato, Hidehiro Oka, Benio Tsuchiya, Sachio Suzuki, Kiyotaka Fujii: "Relationship between the statement of E,N-cadherin and beta-catenin and tumor grade in astrocytomas."J Neuro-Oncol. 57. 187-192 (2002)

Satoshi Utsuki、Yuichi Sato、Hidehiro Oka、Benio Tsuchiya、Sachio Suzuki、Kiyotaka Fujii：“星形细胞瘤中 E,N-钙粘蛋白和 β-连环蛋白的声明与肿瘤分级之间的关系。”J Neuro-Oncol。

Kurata A, Oka H, et al.: "Succressful stent placement for cervical artery dissection associated with the Ehlers-Danlos syndrome"J Neurosurg. 99. 1077-1081 (2003)

Kurata A、Oka H 等人：“成功放置支架治疗与 Ehlers-Danlos 综合征相关的颈动脉夹层”J Neurosurg。