Reexpression of the type 1 insulin-like growth factor receptor inhibits the malignant phenotype of simian virus 40 T antigen immortalized human prostate epithelial cells.
Reexpression of the type 1 insulin-like growth factor receptor inhibits the malignant phenotype of simian virus 40 T antigen immortalized human prostate epithelial cells.
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DOI：
10.1210/endo.138.4.5071
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发表时间：
1997-04
期刊：
影响因子：
4.8
通讯作者：
Stephen R. Plymate;Stephen R. Plymate;Victoria L. Bae;Lisette Maddison;Le Bris S. Quinn;Le Bris S. Quinn-Le-Bris-S.
中科院分区：
文献类型：
--
作者：
Stephen R. Plymate;Stephen R. Plymate;Victoria L. Bae;Lisette Maddison;Le Bris S. Quinn;Le Bris S. Quinn-Le-Bris-S.
1型胰岛素样生长因子受体（IGF-1 R）的表达在前列腺癌相比，在非癌前列腺上皮细胞减少。我们已经证明，作为猴病毒40 T抗原（SV 40 T）永生化的人前列腺上皮细胞系，P69 SV 40 T，经历了从一个不良的致瘤性转化为恶性表型，M12亚系，有一个显着降低IGF-1 R的表达。在本研究中，我们研究了IGF-1 R的再表达对M12细胞恶性表型的影响。使用含有IGF-1 R的7-磷酸酶编码序列LISN的逆转录病毒载体在M12细胞中再表达IGF-1 R，以产生M12-LISN细胞系的几个克隆。作为对照，M12细胞也用不含7-脱氢酶IGF-1 R插入物的逆转录病毒载体（LNL 6）感染（M12-LNL 6克隆）。用M12-LNL 6和M12-LISN细胞中的每一个的两个单独克隆进行功能测定。M12-LISN细胞的每个克隆恢复了在从P69 SV 40 T细胞向M12细胞的转变中丧失的对IGF的增殖反应。此外，当皮下注射时，与M12-LNL 6细胞相比，M12-LISN克隆具有显著降低的生长速率。裸鼠/无胸腺小鼠（P < 0.001）。与M12-LNL 6对照细胞相比，M12-LISN克隆的致瘤性（通过软琼脂中菌落的贴壁非依赖性生长评估）也降低了75%。这些数据表明，IGF-1 R在恶性人前列腺上皮细胞系中的再表达导致肿瘤生长减少和锚定非依赖性集落形成减少，而与对IGF的增殖反应增加无关。IGF-1 R的再表达可能与IGF-1 R介导的细胞增殖和分化功能调节的重新获得有关，这些功能在前列腺上皮细胞转化为恶性表型时丧失。
Type 1 insulin-like growth factor receptor (IGF-1R) expression is decreased in prostate cancer compared to that in noncancerous prostate epithelium. We have demonstrated that as the simian virus 40 T antigen (SV40T) immortalized human prostate epithelial cell line, P69SV40T, undergoes transformation from a poorly tumorigenic to a malignant phenotype, the M12 subline, there is a significant decrease in IGF-1R expression. In the present study, we examine the effects of reexpression of the IGF-1R on the malignant phenotype of M12 cells. The IGF-1R was reexpressed in M12 cells using a retroviral vector containing a 7-kilobase coding sequence for the IGF-1R, LISN, to create several clones of the M12-LISN cell line. As a control, M12 cells were also infected with a retroviral vector (LNL6) without the 7-kilobase IGF-1R insert (M12-LNL6 clones). Functional assays were performed with two separate clones each of M12-LNL6 and M12-LISN cells. Each clone of M12-LISN cells regained the proliferative response to IGF that was lost in the transition from P69SV40T cells to M12 cells. In addition, M12-LISN clones had a significantly decreased growth rate compared to the M12-LNL6 cells when injected s.c. in athymic/nude mice (P < 0.001). Tumorigenicity, as assessed by anchorage-independent growth of colonies in soft agar, was also decreased by 75% in the M12-LISN clones compared to that in the M12-LNL6 control cells. These data demonstrate that reexpression of the IGF-1R in a malignant human prostate epithelial cell line results in decreased tumor growth and decreased anchorage-independent colony formation independent of an increased proliferative response to IGF. Reexpression of the IGF-1R may be associated with reacquisition of the regulation of cellular proliferative and differentiation functions mediated by the IGF-1R that are lost as prostate epithelial cells undergo conversion to a malignant phenotype.