PI3K中p110α和p85α亚基在侵袭性和非侵袭性无功能垂体腺瘤中表达特点
发布时间：2018-12-11 11:07
【摘要】：背景：侵袭性无功能垂体腺瘤是垂体腺瘤中较为特异的一组良性肿瘤,由于肿瘤体积较大,并侵袭周围组织,因此临床上将肿瘤全部切除较困难。术后放疗在部分患者中可以缩小残留肿瘤,然而也可引起垂体功能低下、视神经病变和认知功能障碍等并发症。因此,药物靶向治疗成为抑制无功能垂体腺瘤生长的新方向。PI3K/Akt/mTOR信号通路与细胞的生长、代谢密切相关,在肿瘤的发生发展中起重要作用。PI3K作为PI3K/Akt/mTOR通路的重要因子,分为三种类型,其中ClassI PI3K由一个催化亚基p110(p110α, p110β, p110γ和p110δ)和调节亚基构成,其亚基做为多种肿瘤的药物靶点被研究。然而在无功能垂体腺瘤中,目前尚无PI3K的亚基表达水平的研究。方法：选取2012到2014年就诊于北京协和医院神经外科的无功能垂体腺瘤患者32例,其中侵袭性垂体腺瘤14例(男性5例,女性9例,平均年龄45.5+6.5岁),非侵袭性垂体腺瘤15例(男性9例,女性6例,平均年龄53.0+13.0岁),正常垂体组织3例(男性1例,女性2例,平均年龄58.0岁)。通过免疫组化、Western Blotting、qRT-PCR的方法研究PI3K/AKT/mTOR信号通路中PI3K的催化亚基p110α和调节亚基p85α、PTEN及其下游因子Akt在上述3组样本中的表达变化。结果：免疫组化染色发现,正常垂体组织p110α表达量较侵袭组(p0.05)明显升局。PTEN蛋白在非侵袭组中表达明显高于正常垂体及侵袭性组(p0.05)。Akt染色发现,与正常垂体相比,侵袭组(p0.05)及非侵袭组(p0.001)阳性表达率明显升高；非侵袭组与侵袭组相比升高更明显(p0.01)。Western Blotting显示p85 α蛋白在侵袭组(p0.05)中表达较正常垂体明显升高。在qRT-PCR水平,各指标mRNA表达水平在各分组之间无显著差异。结论：本研究发现,在侵袭性无功能垂体腺瘤中p110α蛋白表达是显著降低的,p85α的表达是升高的。这对下一步PI3K靶向药物在无功能垂体腺瘤中的研究提供实验依据。对于PI3K其他亚基在无功能垂体腺瘤中的表达情况,还有待进一步研究。
[Abstract]:Background: invasive nonfunctional pituitary adenoma is a group of benign tumors in pituitary adenoma. Because of the large size of the tumor and invasion of surrounding tissues, it is difficult to remove the tumor completely clinically. Postoperative radiotherapy can reduce residual tumors in some patients, but it can also cause hypophysis, optic neuropathy and cognitive dysfunction. Therefore, drug targeting therapy has become a new direction to inhibit the growth of nonfunctional pituitary adenomas. PI3K/Akt/mTOR signaling pathway is closely related to cell growth and metabolism. PI3K, as an important factor of PI3K/Akt/mTOR pathway, is divided into three types. ClassI PI3K consists of a catalytic subunit p110 (p110 伪, p110 尾, p110 纬 and p110 未) and regulatory subunit. Its subunits have been studied as drug targets for various tumors. However, there is no study on the subunit expression of PI3K in nonfunctional pituitary adenomas. Methods: from 2012 to 2014, 32 cases of nonfunctional pituitary adenoma were selected from neurosurgery department of Peking Union Hospital, including 14 cases of invasive pituitary adenoma (male 5 cases, female 9 cases, mean age 45. 5 5 years). There were 15 cases of noninvasive pituitary adenoma (male 9 cases, female 6 cases, mean age 53.0 13.0 years) and 3 cases of normal pituitary tissue (male 1 case, female 2 cases, mean age 58.0 years). The expression of the catalytic subunit p110 伪 and the regulatory subunit p85 伪, PTEN and its downstream factor Akt of PI3K in the PI3K/AKT/mTOR signaling pathway were studied by immunohistochemical and Western Blotting,qRT-PCR methods. Results: the expression of p110 伪 in normal pituitary tissue was significantly higher than that in invasive group (p0. 05). The expression of PTEN protein in non invasive group was significantly higher than that in normal pituitary tissue and invasive group (p0. 05). Akt staining). Compared with the normal pituitary gland, the positive expression rates of p0.05 and p0.001 in invasive and non-invasive groups were significantly higher than those in normal pituitary gland. The expression of p85 伪 protein in invasive group was significantly higher than that in normal pituitary group (p0.01). Western Blotting). At the level of qRT-PCR, there was no significant difference in the expression of mRNA among different groups. Conclusion: the expression of p110 伪 protein in invasive nonfunctional pituitary adenomas was significantly decreased and the expression of p85 伪 was increased. This provides the experimental basis for the further study of PI3K targeting drugs in nonfunctional pituitary adenomas. The expression of other subunits of PI3K in nonfunctional pituitary adenomas remains to be further studied.
【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R736.4
，
本文编号：2372426
[Abstract]:Background: invasive nonfunctional pituitary adenoma is a group of benign tumors in pituitary adenoma. Because of the large size of the tumor and invasion of surrounding tissues, it is difficult to remove the tumor completely clinically. Postoperative radiotherapy can reduce residual tumors in some patients, but it can also cause hypophysis, optic neuropathy and cognitive dysfunction. Therefore, drug targeting therapy has become a new direction to inhibit the growth of nonfunctional pituitary adenomas. PI3K/Akt/mTOR signaling pathway is closely related to cell growth and metabolism. PI3K, as an important factor of PI3K/Akt/mTOR pathway, is divided into three types. ClassI PI3K consists of a catalytic subunit p110 (p110 伪, p110 尾, p110 纬 and p110 未) and regulatory subunit. Its subunits have been studied as drug targets for various tumors. However, there is no study on the subunit expression of PI3K in nonfunctional pituitary adenomas. Methods: from 2012 to 2014, 32 cases of nonfunctional pituitary adenoma were selected from neurosurgery department of Peking Union Hospital, including 14 cases of invasive pituitary adenoma (male 5 cases, female 9 cases, mean age 45. 5 5 years). There were 15 cases of noninvasive pituitary adenoma (male 9 cases, female 6 cases, mean age 53.0 13.0 years) and 3 cases of normal pituitary tissue (male 1 case, female 2 cases, mean age 58.0 years). The expression of the catalytic subunit p110 伪 and the regulatory subunit p85 伪, PTEN and its downstream factor Akt of PI3K in the PI3K/AKT/mTOR signaling pathway were studied by immunohistochemical and Western Blotting,qRT-PCR methods. Results: the expression of p110 伪 in normal pituitary tissue was significantly higher than that in invasive group (p0. 05). The expression of PTEN protein in non invasive group was significantly higher than that in normal pituitary tissue and invasive group (p0. 05). Akt staining). Compared with the normal pituitary gland, the positive expression rates of p0.05 and p0.001 in invasive and non-invasive groups were significantly higher than those in normal pituitary gland. The expression of p85 伪 protein in invasive group was significantly higher than that in normal pituitary group (p0.01). Western Blotting). At the level of qRT-PCR, there was no significant difference in the expression of mRNA among different groups. Conclusion: the expression of p110 伪 protein in invasive nonfunctional pituitary adenomas was significantly decreased and the expression of p85 伪 was increased. This provides the experimental basis for the further study of PI3K targeting drugs in nonfunctional pituitary adenomas. The expression of other subunits of PI3K in nonfunctional pituitary adenomas remains to be further studied.
【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R736.4
，
本文编号：2372426
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