TUMORIGENICITY OF SV40 T-ANTIGEN IMMORTALIZED HUMAN PROSTATE EPITHELIAL-CELLS - ASSOCIATION WITH DECREASED EPIDERMAL GROWTH-FACTOR RECEPTOR (EGFR) EXPRESSION
TUMORIGENICITY OF SV40 T-ANTIGEN IMMORTALIZED HUMAN PROSTATE EPITHELIAL-CELLS - ASSOCIATION WITH DECREASED EPIDERMAL GROWTH-FACTOR RECEPTOR (EGFR) EXPRESSION
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DOI：
10.1002/ijc.2910580517
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发表时间：
1994-09-01
影响因子：
6.4
通讯作者：
WARE, JL
中科院分区：
文献类型：
--
作者：
BAE, VL;JACKSONCOOK, CK;WARE, JL
我们的主要目标是：1）开发一个系统的研究前列腺肿瘤的演变;和2）检查表皮生长因子/表皮生长因子受体（EGF/EGFR）途径在前列腺肿瘤进展中的作用。通过转染SV40 T抗原基因（P69SV40 T）而永生化的成人前列腺上皮细胞仅在2.18只小鼠中产生肿瘤，潜伏期为6个月。在裸鼠中生长1或2个周期后，从这些肿瘤中回收的细胞重新注射在2/4和2/3的小鼠中产生肿瘤，潜伏期分别为12、25、25和25天。每个肿瘤的染色体互补是人类的，一致的假二倍体，并保留Y染色体。在这两个锚定独立和贴壁细胞生长测定，EGF刺激增殖约2倍的父母P69SV40 T线和肿瘤亚系。通过Western免疫印迹和流式细胞术分析，肿瘤亚系表达的EFGR蛋白比亲本系少。免疫沉淀显示18和25 kDa TGF-α前体的产生增加，与可检测的EGFR减少平行。亲本P69SV40T系和肿瘤亚系的生长在无血清限定条件下被TGF-α的中和抗体抑制。在增殖和[H-3]胸苷掺入试验中，TGF-α中和抗体的加入始终抑制肿瘤亚系的增殖，超过P69SV40 T。这一发现表明，在人前列腺肿瘤细胞中观察到的致瘤性增加和潜伏期缩短部分是由于TGF-α/EGFR自分泌网络的激活。(C)1994 Wiley-Liss，Inc.
Our primary objectives were to: 1) develop a system for the study of prostatic tumor evolution; and 2) examine the role of the epidermal growth factor/epidermal growth factor receptor (EGF/EGFR) pathway in prostate tumor progression. Adult human prostate epithelial cells previously immortalized by transfection with the SV40 T antigen gene (P69SV40T) produced tumors in only 2.18 mice with a 6 month latency period. Reinjection of cells recovered from these tumors after 1 or 2 cycles of growth in nude mice produced tumors in 2/4 and 2/3 mice with markedly decreased latent intervals of 12, 25, 25 and 25 days each. The chromosomal complement of each tumor was human, consistently pseudodiploid, and retained the Y chromosome. In both anchorage-independent and adherent cell growth assays, EGF stimulated proliferation by approximately 2-fold in both the parental P69SV40T line and the tumor sublines. The tumor sublines expressed less EFGR protein than the parental line, as assessed by Western immunoblotting and flow cytometric analysis. Immunoprecipitation revealed increased production of the 18 and 25 kDa TGF-alpha precursors parallel to decreases in detectable EGFR. The growth of both the parental P69SV40T line and tumor sublines was inhibited by a neutralizing antibody to TGF-alpha under serum-free defined conditions. Inclusion of the TGF-alpha neutralizing antibody consistently inhibited the proliferation of the tumor sublines more than P69SV40T in both proliferation and [H-3]thymidine incorporation assays. This finding suggests that the increased tumorigenicity and decreased latent interval observed among the human prostate tumor cells is partially due to activation of the TGF-alpha/EGFR autocrine network. (C) 1994 Wiley-Liss, Inc.