Suppression of osteosarcoma cell invasion by chemotherapy is mediated by urokinase plasminogen activator activity via up-regulation of EGR1.
Suppression of osteosarcoma cell invasion by chemotherapy is mediated by urokinase plasminogen activator activity via up-regulation of EGR1.
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化疗对骨肉瘤细胞侵袭的抑制是由尿激酶纤溶酶原激活剂活性通过上调 EGR1 介导的。
DOI：
10.1371/journal.pone.0016234
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发表时间：
2011-01-20
期刊：
影响因子：
3.7
通讯作者：
Setoguchi T
中科院分区：
文献类型：
--
作者：
Matsunoshita Y;Ijiri K;Ishidou Y;Nagano S;Yamamoto T;Nagao H;Komiya S;Setoguchi T
化疗后肿瘤反应的细胞和分子机制在很大程度上是未知的。我们发现，低剂量的抗肿瘤药物上调早期生长反应1（EGR1）的表达。EGR1是转录因子的即刻早期基因组的成员，其调节参与细胞增殖、分化和发育的多个基因的转录。据报道，EGR1作为肿瘤促进因子或抑制因子。因此，我们研究了EGFR 1在骨肉瘤中的表达和功能。我们研究了EGFR 1在人骨肉瘤细胞系和活检标本中的表达。我们接下来检查了抗肿瘤剂治疗后EGR1的表达。为了研究EGFR 1在骨肉瘤中的功能，我们在体外和体内评估了肿瘤的生长和侵袭。实时荧光定量PCR结果显示，EGR1在骨肉瘤细胞系和骨肉瘤患者的活检标本中表达下调。此外，EGFR 1在骨肉瘤患者的标本和骨肉瘤细胞系中在抗肿瘤剂治疗后均上调。尽管EGFR 1的强制表达并不能阻止骨肉瘤的生长，但在体外，EGFR 1的强制表达阻止了骨肉瘤细胞的侵袭。此外，EGR1的强制表达促进尿激酶纤溶酶原激活物、尿激酶受体和尿激酶纤溶酶原活性的下调。异种移植小鼠模型显示，EGR1的强制表达阻止了骨肉瘤细胞迁移到血管中。这些结果表明，虽然化疗不能防止骨肉瘤生长的化疗耐药患者，它确实防止骨肉瘤细胞的侵袭通过下调尿激酶纤溶酶原活性通过上调EGFR 1在化疗期间。
The cellular and molecular mechanisms of tumour response following chemotherapy are largely unknown. We found that low dose anti-tumour agents up-regulate early growth response 1 (EGR1) expression. EGR1 is a member of the immediate-early gene group of transcription factors which modulate transcription of multiple genes involved in cell proliferation, differentiation, and development. It has been reported that EGR1 act as either tumour promoting factor or suppressor. We therefore examined the expression and function of EGR1 in osteosarcoma. We investigated the expression of EGR1 in human osteosarcoma cell lines and biopsy specimens. We next examined the expression of EGR1 following anti-tumour agents treatment. To examine the function of EGR1 in osteosarcoma, we assessed the tumour growth and invasion in vitro and in vivo. Real-time PCR revealed that EGR1 was down-regulated both in osteosarcoma cell lines and osteosarcoma patients' biopsy specimens. In addition, EGR1 was up-regulated both in osteosarcoma patient' specimens and osteosarcoma cell lines following anti-tumour agent treatment. Although forced expression of EGR1 did not prevent osteosarcoma growth, forced expression of EGR1 prevented osteosarcoma cell invasion in vitro. In addition, forced expression of EGR1 promoted down-regulation of urokinase plasminogen activator, urokinase receptor, and urokinase plasminogen activity. Xenograft mice models showed that forced expression of EGR1 prevents osteosarcoma cell migration into blood vessels. These findings suggest that although chemotherapy could not prevent osteosarcoma growth in chemotherapy-resistant patients, it did prevent osteosarcoma cell invasion by down-regulation of urokinase plasminogen activity via up-regulation of EGR1 during chemotherapy periods.
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影响因子：
8.4
作者：
Bacci, G;Longhi, A;Picci, P
通讯作者：
Picci, P
DOI：
10.1111/j.1749-6632.1994.tb52846.x
发表时间：
1994-01-01
期刊：
DNA DAMAGE
影响因子：
--
作者：
HAMILTON, JW;MCCAFFREY, J;DOHERTY, KA
通讯作者：
DOHERTY, KA
影响因子：
37.3
作者：
Hirotsu M;Setoguchi T;Sasaki H;Matsunoshita Y;Gao H;Nagao H;Kunigou O;Komiya S
通讯作者：
Komiya S
影响因子：
1.7
作者：
Iwamoto, Yukihide;Tanaka, Kazuhiro;Yamawaki, Shinya
通讯作者：
Yamawaki, Shinya
影响因子：
8
作者：
de Belle, I;Huang, RP;Adamson, ED
通讯作者：
Adamson, ED