Apoptosis in nontumorous and neoplastic human pituitaries: expression of the Bcl-2 family of proteins.
Apoptosis in nontumorous and neoplastic human pituitaries: expression of the Bcl-2 family of proteins.
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DOI：
10.1016/s0002-9440(10)65323-0
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发表时间：
1999-03
期刊：
影响因子：
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通讯作者：
E. Kulig;L. Jin;X. Qian;É. Horváth;K. Kovacs;L. Ştefăneanu;B. Scheithauer;R. Lloyd
中科院分区：
文献类型：
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作者：
E. Kulig;L. Jin;X. Qian;É. Horváth;K. Kovacs;L. Ştefăneanu;B. Scheithauer;R. Lloyd
通过末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记 (TUNEL)、免疫组织化学和蛋白质印迹法，对 95 个非肿瘤性和肿瘤性垂体组织中的细胞凋亡和细胞凋亡调节蛋白 Bcl-2、Bax、Bcl-X 和 Bad 进行了分析。所有组的细胞凋亡指数都相对较低，但垂体癌的细胞凋亡指数比任何其他组至少高四倍。与非怀孕女性的对照对照相比，怀孕和产后女性的垂体细胞凋亡指数高出五倍。术前用奥曲肽或多巴胺激动剂治疗腺瘤并没有显着改变细胞凋亡指数。通过免疫染色检测，Bcl-2、Bax 和 Bcl-X 表达水平最低的是垂体癌。我们实验室使用具有早期大T抗原的复制缺陷型重组人腺病毒开发了永生化人垂体腺瘤细胞系HP75，其细胞凋亡水平比非肿瘤性和肿瘤性垂体高得多。使用转化生长因子 (TGF)-β1 和蛋白激酶 C (PKC) 抑制剂治疗可增加该细胞系的凋亡。用 TGF-β1 和 PKC 抑制剂治疗后对 Bcl-2 家族蛋白的分析显示，与对照组相比，治疗组中的 Bcl-X 降低了 20% 至 30%。这些结果代表了对妊娠和产后病例以及垂体癌中垂体细胞凋亡的首次研究，表明：1）非肿瘤性和肿瘤性垂体组织中的细胞凋亡率较低，但在垂体癌中相对较高，2）垂体肿瘤中 Bcl-2 家族蛋白的表达发生变化，垂体癌中 Bcl-2 表达降低，可能有助于垂体肿瘤的发病机制和/或增殖，以及 3) 培养的垂体肿瘤细胞通过凋亡细胞死亡来响应 TGF-β1 和 PKC 抑制剂。
Analyses of apoptosis and of the apoptosis regulatory proteins Bcl-2, Bax, Bcl-X, and Bad were done in 95 nontumorous and neoplastic pituitary tissues by terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL), immunohistochemistry, and Western blotting. The apoptotic index was relatively low in all groups but was at least fourfold higher in pituitary carcinomas compared with any other groups. Pituitaries from pregnant and postpartum women had a fivefold higher apoptotic index compared with matched controls from nonpregnant females. Preoperative treatment of adenomas with octreotide or dopamine agonists did not change the apoptotic index significantly. The lowest levels of Bcl-2, Bax, and Bcl-X expression were in pituitary carcinomas as detected by immunostaining. An immortalized human pituitary adenoma cell line, HP75, developed in our laboratory using a replication-defective recombinant human adenovirus with an early large T-antigen, had a much higher level of apoptosis than nontumorous and neoplastic pituitaries. Treatment with transforming growth factor (TGF)-β1 and protein kinase C (PKC) inhibitors increased apoptosis in this cell line. Analysis of the Bcl-2 family of proteins after treatment with TGF-β1 and PKC inhibitors showed a 20% to 30% decrease in Bcl-X in the treated groups compared with controls. These results, which represent the first study of apoptosis in pituitaries from pregnant and postpartum cases and in pituitary carcinomas, indicate that 1) the apoptotic rate is low in nontumorous and neoplastic pituitary tissues but is relatively higher in pituitary carcinomas, 2) there are alterations in the expression of the Bcl-2 family of proteins in pituitary neoplasms with a decrease in Bcl-2 expression in pituitary carcinomas that may contribute to pituitary tumor pathogenesis and/or proliferation, and 3) cultured pituitary tumor cells respond to TGF-β1 and PKC inhibitors by undergoing apoptotic cell death.