Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100730, China.
Pituitary. 2014 Dec;17(6):505-13. doi: 10.1007/s11102-013-0535-8.
Adrenocorticotrophic hormone (ACTH)-dependent Cushing's syndrome, called Cushing disease, is caused by a corticotroph tumor of the pituitary gland. Insulin-like growth factor binding protein 6 (IGFBP6), which regulates insulin-like growth factor (IGF) activity and inhibits several IGF2-dependent cancer growths, plays a pivotal role in the tumorigenesis of malignancy, but its roles in ACTH-secreting pituitary adenomas remain unclear.
To investigate IGFBP6 expression in ACTH-secreting pituitary adenomas, and its involvement in tumor growth.
Sporadic ACTH-secreting pituitary adenomas specimens (n = 41) and adjacent non-tumorous pituitary tissues (n = 9) were collected by transphenoidal surgery. IGFBP6 expression was assessed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and validated by Western blotting. Associations of IGFBP6 expression with maximum tumor diameter or Ki-67 labeling index were evaluated in ACTH-secreting pituitary adenomas.
IGFBP6 mRNA and protein expression were both decreased in ACTH-secreting pituitary adenomas, compared to adjacent non-tumorous pituitary tissues (P < 0.01). IGFBP6 expression was correlated inversely with maximum tumor diameter (Rho = -0.53, P < 0.0001) and Ki-67 levels (Rho = -0.52, P < 0.05). Moreover, IGFBP6 downregulation activated PI3 K-AKT-mTOR pathway in ACTH-secreting pituitary adenomas.
IGFBP6 attenuation in ACTH-secreting pituitary adenomas is associated with tumor growth, through activation of PI3K-AKT-mTOR pathway. The finding underlies IGFBP6 roles in Cushing disease and would potentially provide a novel target of medical therapies.
促肾上腺皮质激素（ACTH）依赖性库欣综合征，又称库欣病，是由垂体的促皮质细胞瘤引起的。胰岛素样生长因子结合蛋白 6（IGFBP6）调节胰岛素样生长因子（IGF）的活性，并抑制几种 IGF2 依赖性癌症的生长，在恶性肿瘤的发生中起着关键作用，但它在 ACTH 分泌性垂体腺瘤中的作用仍不清楚。
研究 IGFBP6 在 ACTH 分泌性垂体腺瘤中的表达及其在肿瘤生长中的作用。
通过经蝶窦手术采集散发性 ACTH 分泌性垂体腺瘤标本（n=41）和相邻非肿瘤性垂体组织（n=9）。采用实时定量逆转录聚合酶链反应（qRT-PCR）评估 IGFBP6 表达，并通过 Western blot 验证。评估 IGFBP6 表达与 ACTH 分泌性垂体腺瘤最大肿瘤直径或 Ki-67 标记指数的相关性。
与相邻非肿瘤性垂体组织相比，ACTH 分泌性垂体腺瘤中 IGFBP6 mRNA 和蛋白表达均降低（P<0.01）。IGFBP6 表达与最大肿瘤直径呈负相关（Rho=-0.53，P<0.0001）和 Ki-67 水平呈负相关（Rho=-0.52，P<0.05）。此外，IGFBP6 下调激活了 ACTH 分泌性垂体腺瘤中的 PI3K-AKT-mTOR 通路。
ACTH 分泌性垂体腺瘤中 IGFBP6 的衰减与肿瘤生长有关，通过激活 PI3K-AKT-mTOR 通路。这一发现为 IGFBP6 在库欣病中的作用提供了依据，并可能为医学治疗提供新的靶点。
