Down-regulation of TGF-beta1 production restores immunogenicity in prostate cancer cells.

Down-regulation of TGF-beta1 production restores immunogenicity in prostate cancer cells.
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DOI:
10.1054/bjoc.2000.1257
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发表时间:
2000-08
影响因子:
8.8
通讯作者:
Lee C
Lee C
中科院分区:
医学1区
文献类型:
--
作者:
Matthews E;Yang T;Janulis L;Goodwin S;Kundu SD;Karpus WJ;Lee C

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本研究的目的是确定非免疫原性的邓宁大鼠前列腺癌细胞系MATLyLu是否可以通过减少内源性TGF-β1的产生而变得免疫原性。将含有TGF-β1反义取向DNA序列的表达构建体(TGF-β1反义)稳定转染到MATLyLu细胞中。转染后,细胞中TGF-β1的含量从70 pg / 2 × 104细胞减少到10 pg / 2 × 104细胞,体外3h -胸苷结合率增加3 - 5倍。将肿瘤细胞皮下注射到同基因雄性宿主(哥本哈根大鼠)中,野生型MATLyLu细胞和转染对照构建的细胞的肿瘤发生率为100%(15/15),而转染TGF-β1反义的细胞的肿瘤发生率为43% (9/21,P≤0.05)。然而,将细胞注射到免疫缺陷宿主(胸腺裸鼠)中,野生型MATLyLu细胞和转染对照构建体的细胞的肿瘤发展发生率均为100%(10/10),转染TGF-β1反义的细胞的肿瘤发展发生率为90%(9/10)。这些观察结果支持MATLyLu细胞具有免疫原性的概念,当内源性TGF-β1的产生下调时。©2000癌症研究运动
The objective of this study is to determine if a non-immunogenic Dunning’s rat prostate cancer cell line, MATLyLu, can become immunogenic by reducing the endogenous production of TGF-β1. An expression construct containing a DNA sequence in an antisense orientation to TGF-β1 (TGF-β1 antisense) was stably transfected into MATLyLu cells. Following transfection, cellular content of TGF-β1 reduced from 70 to10 pg per 2 × 104cells and the rate of in vitro3H-thymidine incorporation increased 3–5-fold. After subcutaneous injection of tumour cells into syngeneic male hosts (Copenhagen rats), the tumour incidence was 100% (15/15) for the wild type MATLyLu cells and cells transfected with the control construct, but only 43% (9/21, P≤ 0.05) for cells transfected with TGF-β1 antisense. However, when cells were injected into immunodeficient hosts (athymic nude rats), the incidence of tumour development was 100% (10/10) for both the wild type MATLyLu cells and cells transfected with the control construct and 90% (9/10) for cells transfected with TGF-β1 antisense. These observations support the concept that MATLyLu cells are immunogenic, when the endogenous production of TGF-β1 is down-regulated. © 2000 Cancer Research Campaign
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