RESEARCH FOR MOLECULAR MECHANISM OB METASTASIS IN OVARIAN CANCER -USING OF ORTHOTOPIC OVARIAN CANCER MODEL.

卵巢癌OB转移的分子机制研究——利用原位卵巢癌模型。

• 批准号: 12671586
• 负责人: YOSHIDA Yoshida
• 金额: $ 0.96万
• 依托单位: Fukui Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671586/
• 关键词: OVARIAN CANCER; LAMININ; ORTHOTOPIC MODEL; MPTASTASIS; 転移

Our goal was to define the active sites on laminin important in ovarian tumor growth and spread and determine if these active sites regulated survival genes. Here we investigated the possible mechanism by which laminin-1 exerts its promotion of tumorigenesis and metastasis. Cells were co-injected with laminin-1 and active laminin peptides from feed (A13 : RQWQVAYTIIKA, A12 : WVTVTLDLRQVFQ, AG73 : LQVQLSIR, IKVAV) and 6 (YIGSR) chains. Ovarian tumor growth and metastasis were increased in the presence of laminin-1 plus either AG73 peptide, IKVAV, or A13, and were significantly reduced in the presence of A12 or YIGSR. Expression of Bcl-2 and Mdm2 was higher by 3.5 fold and about 100-fold, respectively, in ovarian tumors grown in the presence of laminin-1 compared to tumors grown in the presence of gelatin. Moreover, peptides A13 and AG73 further elevated Bcl-2 expression by 6-fold and 7-fold respectively, while IKVAV yielded expression similar to laminin-1. YIGSR and A12 reduced the expression of Bcl-2 by 7- and 3-fold, respectively, compared to treatment with laminin-1. A13 and AG73 increased Mdm2 expression by 1.8 and 1.3 fold, respectively, while IKVAV, A12, and YIGSR were without effect. Thus, laminin-1 exerts its proliferative effect on the development of ovarian tumor via upregulation of survival genes such as Bcl-2 and Mdm2, which can block the activity of P53. Peptides A13 and AG73 (which increased tumor growth and spread) enhance the expression of these genes and A12 and YIGSR (which decrease tumor growth and spread) attenuate their expression. IKVAV probably enhances tumor growth and metastasis by another mechanism,

我们的目标是定义在卵巢肿瘤生长中重要的层粘连蛋白上的活性位点，并确定这些活跃部位是否调节生存基因。在这里，我们研究了层粘连蛋白1促进肿瘤发生和转移的可能机制。将细胞与饲料（A13：RQWQVAYTIIKA，A12：WVTVTVTLDLRQVFQ，AG73：LQVQLSIR，IKVAV）和6（YIGSR）链共注入。在存在A12或YIGSR存在下，在存在层粘连蛋白1和AG73肽，IKVAV或A13的情况下，卵巢肿瘤的生长和转移增加了。与在存在明胶存在下生长的肿瘤相比，在存在层粘连蛋白1的卵巢肿瘤中，Bcl-2和MDM2的表达分别高3.5倍和约100倍。此外，肽A13和AG73分别以6倍和7倍的速度将Bcl-2表达升高，而IKVAV产生的表达类似于层粘连蛋白-1。与用层粘连蛋白1的治疗相比，YIGSR和A12分别将Bcl-2的表达降低了7和3倍。 A13和AG73分别将MDM2表达增加1.8和1.3倍，而IKVAV，A12和YIGSR无效。因此，层粘连蛋白-1通过上调生存基因（例如Bcl-2和MDM2）对卵巢肿瘤的发育产生增殖作用，这可以阻止p53的活性。肽A13和AG73（增加肿瘤生长并扩散）增强了这些基因的表达，A12和YIGSR（减少肿瘤的生长和扩散）会减轻其表达。 IKVAV可能通过另一种机制增强肿瘤的生长和转移，

项目成果

Yosio Yoshida et al.: "Role of laminin in ovarisn caneer fumor growth and metastasis via regalotion of Mdm2 and Bel-2 expression"International Journal of Oncology. 18. 913-921 (2001)

Yosio Yoshida 等人：“通过调节 Mdm2 和 Bel-2 表达，层粘连蛋白在卵巢癌肿瘤生长和转移中的作用”国际肿瘤学杂志。

Yoshida Yoshio et al: "Role of laminin in cvarian cancer tumor growth and metastasis via regulation of Mdm2 and Bcl-2 expression"International Journal of oncology. 18(in press). (2001)

Yoshida Yoshio等人：“层粘连蛋白通过调节Mdm2和Bcl-2表达在卵巢癌肿瘤生长和转移中的作用”国际肿瘤学杂志。

Yoshida Y. et al.: "Role of laminin in ovarian cancer tumor growth and metastasis via regulation of Mdm2 and Bcl-2 expression"Int. J. Oncology. 18. 913-921 (2001)

Yoshida Y.等人：“层粘连蛋白通过调节Mdm2和Bcl-2表达在卵巢癌肿瘤生长和转移中的作用”Int。

Yoshio Yoshida et al.: "Role of laminin in ovarian cancer tumor growth and metastasis via regulation of Mdm2 and Bcl-2 expression"International Journal of Oncology. 18. 913-921 (2001)

Yoshio Yoshida 等人：“层粘连蛋白通过调节 Mdm2 和 Bcl-2 表达在卵巢癌肿瘤生长和转移中的作用”国际肿瘤学杂志。